This month, Imperial Stem Cell and Regenerative Medicine Network (ISRMN) interviewed Dr Clara Lopes Novo, a Project Research Scientist at the Francis Crick Institute, Honorary Research Fellow at Imperial College London and ISRMN member.

Interviewee: Dr Clara Lopes Novo
Interviewer: Priyanka Peres (priyanka.peres22@imperial.ac.uk)

Priyanka: Good afternoon Dr Novo, thank you so much for meeting with me. I am very excited to discuss your research with you - it is a fascinating exploration of what drives genomic instability in the genome and epigenome, and you've chosen stem cells as your main model of study, which is particularly interesting to us. Before we discuss that, what got you started in science and what has been your journey so far?

Dr Novo: You’re welcome, and yes, it's a funny story. Why science? Ever since I was born, I have always been very curious about science and biology in particular. When I was 11, I went to an exhibition in the Atomium building in Brussels. There, they had a molecule of DNA stretching from one wall to another, which was labelled as “the code of life”. I was amazed and I even asked my biology teacher for further reading about DNA. From that moment I decided I wanted to be a scientist and study genetics.

Priyanka: That's so exciting. It's so interesting how our experiences as children continue to motivate us in the future.

Dr Novo: Yes, especially that phrase: “This molecule encodes the meaning of life”, in all organisms, in everything, every life has a code. I thought that was amazing.

Priyanka: Did that mean you studied biology as an undergraduate?

Dr Novo: Yes. I did biology with a heavy focus on genetics. Although I did study other subjects within biology, genetics has been my focus since undergrad, and my PhD was in human molecular genetics as well. So yes, this has been my area of research since the beginning.

Priyanka: And how did you find yourself here, studying genomic instability?

Dr Novo: That again, is a funny story. So I study junk DNA: the repetitive, noncoding sections of the genome. Although we now know it is expressed, at the time, ‘junk DNA’ was seen as non-functional. The reason I got interested in this area was one of the first courses I had in
university. The lecturer was talking about telomeres and she said “This is part of junk DNA but it's also important for cancer and ageing”. I was baffled - how could something be “junk” DNA and yet important for ageing, cancer and more? So I got really interested in telomeres and that's what I first studied in my postdoc. During that time, I wrote a review about the 3D organisation of the nucleus and telomeres specifically. That was the first time that I shifted my perspective of genetics from 2D to 3D. We tend to think of DNA as a linear molecule but it's not, it has a complex 3D structure. I realised that that's what I am interested in - the three-dimensional nucleus and its impact on embryonic development and stem cells.

Priyanka: Why is it that you chose stem cells specifically, to study 3D organisation?

Dr Novo: Well, during early embryonic development, in the pre-implantation embryo, the chromatin is very plastic, as these cells can develop into any cell type - the 3D organisation hasn't been defined yet. Then, cells start exiting pluripotency and priming for different cell fates and each cell type has a very defined 3D organisation. So before that point, there is a small window of development. If you want to understand what regulates how the genome is organised in 3D, this is the developmental window that you need to study.

Priyanka: That's very interesting. Within this field, what are you currently working on?

Dr Novo: So I have continued to study junk DNA or heterochromatin - telomeres and pericentromeres. These are regions of the genome that are normally very compact and have silencing epigenetic marks. Except in stem cells - where they are still compact and heterochromatic. My work aims to understand why: why pluripotent stem cells require these regions or why they can tolerate these regions being less heterochromatic. We found that if we force compaction and increase heterochromatin in these regions in embryonic stem cells it leads to genetic instability. Based on this, we believe there is a need for less compaction in these regions in pluripotent embryonic stem cells. There seems to be a need to maintain this junk DNA, this heterochromatin, in a more relaxed manner. Currently, I am studying the role of telomeres and pericentromeres in relation to genomic instability in mouse embryonic stem cells.

Priyanka: And what is your prediction of the role that they might have?

Dr Novo: Given that these regions are very heterochromatic and their neighbouring genes are often silenced, my hypothesis is that by allowing these regions to be less heterochromatic in stem cells, they don’t silence nearby genes as strongly. Then, once the cells exit pluripotency and these regions become more heterochromatic, it creates ‘heterochromatin hubs’ where any genes in the vicinity by 3D structure (through genome looping or other structures) are silenced and repressed.

Priyanka: So it would be a kind of mass silencing of genes that control pluripotency?

Dr Novo: Exactly, just by the folding of the genome, which would increase gene silencing in these hubs. Genome folding also happens differently in the different cell types. And so you have different sets of genes potentially being silenced by these heterochromatin hubs.

Priyanka: What do you envision as the impact of this work in the future?

Dr Novo: There are actually two main points for this. One of them is that all these rearrangements of the 3D organisation - the compaction and the heterochromatinization of junk DNA - happen normally during embryonic development, but the reverse happens during tumorigenesis. Most tumours have relaxed junk DNA and less heterochromatin. Telomeres are also elongated to grant immortality to cancer cells and overall, the 3D organisation of the cell type of origin is lost in the tumour-derived cells. This represents a loss of 3D memory in the cell. So we hope that by understanding the processes that naturally occur during embryonic development, we may actually understand how these processes can be deregulated and contribute to tumorigenesis.

The other potential future impact of this work comes from the link to genetic instability. Early compaction of these regions often leads to aneuploidy in the cell. Aneuploidies are the most common defect observed in spontaneously aborted embryos, which are not able to implant in the uterine wall. We don’t fully understand this process: stem cells do have relaxed DNA repair pathways that allow them to continue dividing but clearly some process is still checking for genetic or chromosomal defects such as aneuploidy. We believe that understanding the epigenetic regulation of heterochromatin and genetic stability in the embryo could provide invaluable biomarkers for IVF treatments. We could potentially identify which embryos look like they have a more promising 3D organisation of their genome. So this research has potential for an impact on reproductive biology as well. However, there is still a lot to learn about what regulates the stability of the genome in preimplantation embryos. We also know that in ageing women, the processes that maintain the 3D organisation of the
genome and the epigenetics - the positions of heterochromatin marks - start decreasing efficiency. In an ageing population such as ours that starts having children at a later age, I think research into reproductive biology will become increasingly important.

Priyanka: Fascinating, thank you for explaining that. What would you say has been the most challenging aspect of this work for you?

Dr Novo: I would say - the dogmas in the field. So, for example, heterochromatin was thought to be very compact and very static in 3D, but new insights from pre-implantation mouse embryos have shown that it is actually quite mobile and a lot more flexible than we anticipated for many years. A big challenge has been to get the scientific community to understand that.

Priyanka: On the other hand, what's been the most rewarding or exciting part of it for you?

Dr Novo: Very similar - it's through challenges that we move forward, after all. The most rewarding has been to speak with people and watch them change their minds or consider a new perspective, based on our data, especially our live imaging of heterochromatin.

Priyanka: Thank you so much. This has been incredibly interesting and all the best to you with
all of your work. Thank you so much for speaking with me and the ISRMN

This month ISRMN spoke with Dr Tamas Korcsmaros, who is a Senior Lecturer in Intestinal Epithelial Biology and Co-lead of the NIHR Imperial BRC Organoid Facility.

1. What first drew you to science research and what has been your journey so far?

I started my scientific research at high school. Luckily in Hungary there has been an initiative that allow high school students to go into universities and try themselves out doing research in a supportive environment. Originally, I started working in an experimental biochemical project looking at the redox adaptation of the liver. I did a BSc project about that as well but by the time I started my master project in the same lab I started working with computational approaches. I started to be very interested about network science and network biology, and the translational aspect of looking at complex systems, identifying new drug targets and understanding better pathologic rewiring. At the beginning, I thought that it will be a quick computational journey, and I will go back to the lab to continue doing experiments but basically since then most of the time I'm working through a computer, to analyse and visualise data. After the PhD, I kind of skipped the post doc part of my career. I already during the PhD was supervising students and at the end of the PhD, I won an innovation grant that allowed me to establish a small group. It all happened back in Budapest in Hungary. I also started teaching, developed a couple of bioinformatics courses there. Then in 2014, I received a special BBSRC fellowship to move to Norwich and to work in two institutes, the Earlham and the Quadram institutes. The Earlham is a computational biology, systems biology institute while the Quadram is focusing on the gut microbiome. These two approaches/topics were really relevant for me as I wanted to generate data and connect dry science with the wet lab approaches. After I finished this five-year fellowship, I became a tenure track group leader there. During this period, we established multiple computational resources that are currently used by thousands of researchers per month. We also developed experimental methods to study gut related processes, and this is where I met with a fantastic stem cell based technology called organoids.

2. What research do you do and what do you think the impact is? As a (role) why are you interested in stem cells?

One and a half years ago, I moved to Imperial College as senior lecturer at the Division of Digestive Diseases. Here, in one place I'm able to combine both the computational and the experimental projects I'm doing. In particular I'm working with inflammatory bowel disease which is a complex chronic disease for which we don’t really know the underlying pathogenesis. There have been lots of studies done in mouse models, in human cell cultures and in patient cohorts but with limited clinical success. Intestinal organoids are providing a gap filling and much needed aspect, namely to study key epithelial cells, such as Paneth cells or goblet cells that normally you can’t keep in cell culture. Using specifically differentiated organoids, our group was the first to reconstruct the regulatory network of these cells (ie., to show how genes specifically in these cells are regulated. This was the project where I realised the promise of combining patient-derived gut organoids with omics approaches to gain new understanding of what is going bad in inflammatory bowel disease. Currently, we continue develop omics and imaging approaches of organoids as well create computational data integration pipelines for the community. More details can be found on our group’s website.

3. What are your next steps?

Another role I have at Imperial, beside my research group is co-leading the recently established NIHR Imperial BRC Organoid Facility. In this facility, we are not only working with gut organoids but many other organoids, including iPSC derived organoids (lead by Tamir Rashid for liver organoids and Harry Leitch for general iPSC organoid generation). We are supporting and we are going to support many other departments and research groups in Imperial. This is a very exciting and new opportunity not only for me but I think for the College as there have already been lots of great projects and papers showcasing the brilliant resources already available in Imperial. With this facility we are trying to support this and facilitate connections between existing groups from engineering to clinical research groups. My main goal is to streamline the process from collecting patient samples, growing organoids, executing very complex experiments with them, and then doing multi-omics analyses on these organise or high content imaging. The finally our computational and scalable approaches will interpret, analyse and visualise the data for great publications and to increase their translational impact.

4. What was your most fun or inspirational time in the lab/ science?

Standing in front of a big smart screen with my group and interactively analysing a very complex dataset. I like working with different types of people, and we support each other in many different ways. When we have an idea, we test it together, criticise and improve it. Doing science together in teams is fun!

5. What was your biggest career or scientific disappointment and how did you overcome it?

One of my very first papers (my PhD paper practically) took me two years to get published. It was a great story, and got reviewed in very nice journals but always got rejected for reasons that I felt was unjustified. One of the reviewers, in a very-very good journal for example wrote that ‘I did not have enough time to check the whole manuscript, so I can only provide feedback on the first results section’. As a recently started researcher this was very disappointing, and I learned a lot about rejection and being unsuccessful for a longer period. Eventually, I got used to these, accepted them, tried to learn from each as much as possible, and move on quickly. Later on, I realised that experiencing these early was very helpful to become resilient to these failures, which are unfortunately inherent part of a scientist’s career.

6. What has been your favourite outreach activity and what made it stand out?

Recently, at Imperial Lates, we started experimenting to show our computational work with VR glasses. It was a big success, and finally I had the feeling that this is a way we can show our “dry” work to other colleagues and the general public. I would like to invest more on these, and improve the games we are providing to illustrate better how big data can help understanding stem cells and organoids.

This month ISRMN spoke with Uta Griesenbach and Eric Alton, who jointly lead the Gene Therapy Group at the NHLI and have, for over 25 years formed a successful partnership combining research and clinical expertise.

1. What first drew you to science research and what has been your journey so far?

Uta: Gene therapy and in particular gene therapy for cystic fibrosis drew me to science. I did my undergraduate degree in Germany and then looked for PhD positions abroad. I did my PhD with Lap-Chee Tsui at the Hospital for Sick Children in Toronto. The lab was involved in identifying the cystic fibrosis gene in 1989.When I joined the lab there was big excitement now kowing the genetic defect causing cystic fibrosis, which made the development of gene therapy possible. Cystic fibrosis is one of the earliest diseases that gene therapy research has been initiated for. I joined Imperial in 1997 as a postdoc in Eric’s lab and from there I have developed my research career and portfolio working on gene therapy.

Eric: I am a respiratory doctor by training and joined the Brompton Hospital in 1983 where I met someone who became my mentor, Duncan Geddes. I was tasked with developing a new diagnostic test for cystic fibrosis measuring the altered electricity on the surface of the nose and lungs because of the defective CFTR protein and that’s how I got into cystic fibrosis. This test is now used in both an adult and paediatric clinic at the Brompton Hospital specifically organised for difficult-to-diagnose patients. I can also be used to see whether gene therapy is making a difference and changing the electricity back to normal values and this is how I was introduced to the field of gene therapy. I worked with Duncan for 25 years and started my lab at Imperial about 30 years ago. We have also been working with many other colleagues from Oxford and Edinburgh and together formed the the UK Respiratory Gene Therapy Consortium which I have the privilege to lead. Reflecting on my journey as a clinician involved in research, I can say that it is highly rewarding but also that there are easier routes than doing academic medicine (with writing papers and grant applications). Clinicians partnering with world-class scientists works very well and we need more of these partnerships

2. What research do you do and what do you think the impact is? As a (role) why are you interested in stem cells?

Uta: Our research is all related to gene therapy for lung diseases, mainly cystic fibrosis but also alpha 1 antitrypsin deficiency and alveolar pulmonary fibrosis (PAP). Our group is part of the UK Respiratory Gene therapy Consortium and colleagues work on a range of other disease indication. Over the years we have worked with many viral and non-viral gene transfer agents. Most importantly we have developed a lentiviral vector platform which is very efficient in delivering genes to the lung. We have recently partnered and sold this platform to Boehringer Ingelheim. In the context of cystic fibrosis, we are not targeting stem cells because in the airways the stem/progenitor cells are hidden underneath the epithelium and not accessible. However, in alpha 1anti-trypsin deficiency and PAP where we are targeting the alveolar region, stem cells such as type II cells become a good target and we are interested to study them further.

Eric: The consortium has a big impact on the field of cystic fibrosis as the world’s largest academic group doing cystic fibrosis gene therapy. We were the first group to show gene therapy benefits lung function in these patients and have now extended the scope of this research to non-CF disease indications.

3. What are your next steps?

Eric: With Boehringer Ingelheim we are doing the world’s first clinical trial with a lentiviral vector for cystic fibrosis. For the other diseases we are trying to spin-out a company to bring new money into the field to do the clinical trials, which are very expensive, to take the research forward. Interacting with industry and forming a spin out were new experiences for us. It’s a different world which takes time getting used to and with which we are getting valued help from colleagues across Imperial.

Uta: We are now deciding how much involvement we will have with the spin out and figuring out how to potentially combine our academic roles with parttime chief scientific / medical officer roles in the spin out.

4. What was your most fun or inspirational time in the lab/ science?

Uta: The promise of making the health of patients better is inspirational. It has been very exciting to take develop a product such as our lentiviral vector platform from the lab bench to patients and ultimately sell to large pharma.

Eric: I share Uta’s views. The whole reason for doing this journey is to translate research to patients. For a scientist like Uta, having such a translational angle is fairly unique. I can’t pinpoint one moment because I really enjoy the fact that day to day there are always new challenges, things don’t go according to plan. The fun comes from working together as a big team, not only within Imperial but together with the Consortium colleagues for a long period of time and jointly trying to overcome some of these difficult hurdles from day to day.

5. What was your biggest career or scientific disappointment and how did you overcome it?

Uta: I am disappointed when we don’t get funding for projects we believe in. Admittedly sometimes we are over-enthusiastic, and the reviewers may be right to reject the grant. However, due to limited funding budgets good applications are often rejected in what is becoming a more and more competitive funding environment.

Eric: I am not sure I can tell you there was a big disappointment. There have been lots of hiccups as we go along. Obviously, I would have loved the liposome-based gene therapy for cystic fibrosis clinical trial to show more improvement than it did in lung function but overall, I have enjoyed my career and enjoyed the challenges. In an academic career, things go up and down all the time; it’s like share prices.

6. What has been your favourite outreach activity and what made it stand out?

Uta: We do carry out a large number of outreach activities. If I have to pick a favourite it will be outreach activities with children and schools, seeing the enthusiasm and smiles of GCSE students when we explain what gene therapy is very rewarding.

Eric: We also take students in the summer who want work experience in the lab and we have had lots of good feedback. They often come with the question: should I be a scientist or a doctor? They have the potential to do both and this experience helps them decide, which is very rewarding.

This month ISRMN spoke with Mr Jiarui (Henry) Xu. 
He is a PhD Student at the Department of Life Sciences.

1. What first drew you to science research and what has been your journey so far?

I first became interested in research during the ‘research abroad’ year as an undergraduate student when I did a year-long placement at ETH Zurich. The process of problem-solving, doing interesting work, and the prospect that my findings might reveal parts of the unknown were some of the factors that push me into research. Since then, I have also worked as a research assistant in a haematopoiesis background. And now I am 7 months into my PhD study in the Luis lab. 

2. What research do you do and what do you think the impact is?

My research focuses on the mechanisms that regulate the quiescence and proliferation of haematopoietic stem cells (HSCs) in the bone marrow niche. The hope is to identify such mechanism which may potentially serve as therapeutic targets in the future. I became interested in stem cells towards the end of my undergraduate study and this interest was re-affirmed while working as a research assistant. There is still much we don’t understand about the mechanisms and how they interplay in regulating the activity of HSCs. The potential impact of further clinical translation based on the underlying mechanisms discovered makes me excited about stem cell research. 

3.  What are your next steps? 

My immediate goal is to continue and complete my PhD project. As with most PhD students halfway through or towards the end of their studies, it will become clearer which career path one would like to take after the PhD. 

4. What was your most fun or inspirational time in the lab/science?

Good teamwork and discussion of ideas with team members and other collaborators can be quite fun and very inspirational. However, I confess it will be difficult to pick a particular moment in time that was most fun or inspirational. 

5. What was your biggest career or scientific disappointment and how did you overcome it?

During a research project as an undergraduate student, cloning (plan A) failed despite months of attempts. Through extensive troubleshooting, it turns out that the materials provided to us were incorrect. It was very disappointing after months of work. However, there was no time to resolve this issue as we approach the end of the project. Fortunately for the 4 of us in the same group, we had a safe plan B option moving almost in parallel with plan A. It literally saved us and still allowed us to proceed and address most of the research questions. 

6. What has been your favourite outreach activity and what made it stand out?

I have volunteered as a GCSE and A-level Biology tutor in several academies in London. The works usually involve helping students understand difficult knowledge blocks from their normal lessons where they cannot get individual support. Bursts of elation as they cleared the hurdles that confused them and their appreciation for my help altogether made it a genuinely rewarding experience. I strongly believe that equal access to education, including individual tutoring support, to students from all backgrounds, is very important. 

This month ISRMN spoke with Ms Liliana Brito. 
She is a final year PhD Student at National Heart and Lung Institute.

1. What first drew you to science research and what has been your journey so far?

Right after high school, I decided that I would like to be a researcher in the biomedical sciences field. I remember feeling the social pressure to go to med school because I had the grades to do that, but I knew I would prefer to work in a laboratory. Therefore, I completed my bachelor studies in Cellular and Molecular Biology and afterwards, I did my MSc in Biotechnology. Staying in Portugal, where I am from, was an option, but I decided to try my chances abroad. I was selected for a research internship in Madrid, where I worked in the Instituto de Salud Carlos III under the supervision of Dr Monica Amblar. Until here, I gained experience in bacterial and mammalian cell models and my interest in non-viral gene therapy increased. Fortunately, in 2017, I was selected to start the British Heart Foundation 4-year MRes/PhD programme at Imperial College London, under the supervision of Professor Molly Stevens, Professor Sian Harding, Professor Nadia Rosenthal, and Doctor Michela Noseda. Here, I had the opportunity of applying my cellular and molecular biology background with the bioengineering field to study cardiac regeneration using a gene therapy approach.

2. What research do you do and what do you think the impact is?

I am currently finishing my PhD where I investigated the potential of enhancing the paracrine signalling of the epicardium to promote heart regeneration. Cardiovascular diseases continue to be one of the significant burdens for healthcare systems and there is the need to find a treatment to regenerate the heart after a heart attack. During my PhD I was primarily focused on developing a non-viral gene therapy platform for the epicardium to promote the proliferation of different cardiac cell types, such as stem cells-derived cardiomyocytes.

3.  What are your next steps? 

During my PhD, I had the great opportunity to participate in several extracurricular activities. Imperial College allowed me to be involved in this network (ISRMN), teaching, public engagement, and fundraising. I was also part of the Executive Committee of the Portuguese Association of Students and Researchers in the UK (PARSUK). These experiences increased my interest in exploring a STEM educational career path, and I am currently looking for a job. My goal in my next step is to integrate my scientific expertise with the educational development of the society.

4. What was your most fun or inspirational time in the lab/science?

I consider good collaborative work the most positive experience we can have as scientists. We share the responsibility of our projects; we brainstorm and learn; we celebrate scientific achievements, and we support each other when experiments do not work. I am grateful for having contributed to different researchers’ projects and for having received their contributions as well in my research. Thank you colleagues and collaborators!

5. What was your biggest career or scientific disappointment and how did you overcome it?

I feel that academic researcher careers are getting increasingly competitive, and I also started feeling the pressure to do it right in my PhD to succeed. This pressure was not imposed by my supervisors but by myself and the competitive job market we are surrounded by. At some point, it started affecting my mental health and I had to seek help. With the support of a psychologist and my supervisors, I worked on myself, and I learnt how to deal with my expectations and emotions. It is becoming crucial to know our limits and when we need help. Fortunately, academic institutions are nowadays more aware of this problem and investing more resources in helping their academic community.

6. What has been your favourite outreach activity and what made it stand out?

I have been volunteering as a science communicator through the Native Scientist. The Native Scientist organizes workshops in schools that promote science and language integrated learning. The workshops bring together international scientists and school pupils who speak more than one language. These workshops are not only an excellent opportunity to improve our lay science communication skills, but I also felt closer to my home country since we delivered them in our native language. You can read here a NHLI blog post I wrote about my participation in one of these workshops.

Additionally, as part of the Stevens Group, my colleague Sara Carvalho and I developed the outreach project “Tell me what you see”, funded by the Biochemical Society Outreach Grant. Since it was during the pandemic, all the sessions were virtual. We aimed to promote inclusivity by challenging the students with a real-time quiz to assess their perception of who could be a scientist and, afterwards, by presenting a video where various scientists said, “I am a Scientist” in their mother tongue (more than 10 languages were represented). After that, we asked the students to create a piece of artwork about unknown scientific images. With this approach, we aimed to engage the students visually and increase their curiosity about the real meaning of the images. Meanwhile, we also intended to stimulate their creativity to inspire our science. In the second session, the researchers delivered short science classes presenting the science behind the images and prizes were gifted to the most creative artworks. Feedback from the teachers and students was highly positive.

 Find out more about Ms Liliana Brito's research

This month ISRMN spoke with Dr Michela Noseda. 
She is a Lecturer in Cardiac Molecular Pathology at National Heart and Lung Institute.

1. What first drew you to science research and what has been your journey so far?

It was during medical school that I started to be interested in research. Indeed, although in Italy there is not a structured system to allow medical students to do basic research I joined a research lab and took time to gain experience. Scientifically, I have started with paediatric oncology and cell cycle studies moving to angiogenesis and via blood vessels, I reached the heart. Cardiac disease and heart failure is the focus of my research for many years now.

2. What research do you do and what do you think the impact is?

The focus of my research is heart failure. My teamwork is based on the study of human cardiac tissue complemented by human iPSC-derived cardiomyocytes and animal models. By applying novel ‘omics technologies including single cell RNA-seq and spatial transcriptomic to study the human heart, we provide a unique understanding of cardiac disease and also the healthy heart at an unprecedented resolution. These technologies allow us to explore and define new and rare cell types including stem and progenitor cells. Likewise reconstructing the cell-cell interactions and cell co-localization will provide a way to identify potential stem/progenitor cell niches. The prediction of novel pathways is then validated using human iPSC-derived cardiomyocytes. 

3. What are your next steps? 

Expand the work to paediatric human hearts, a crucial step relative to the definition of cardiac regenerative potential which we know is minimal in the adult versus paediatric hearts that might have a more plastic phenotype.

4. What was your most fun or inspirational time in the lab/science?

As geeky as it can sound, I love the late nights at the lab finishing that crucial long experiment. Seeing beating human iPSC-derived cardiomyocytes put a smile on my face every single time. The intensity of working with a whole human heart of a donor is a great responsibility and of great inspiration to ensure one can obtain the highest quality of data and the most possible information.

5. What was your biggest career or scientific disappointment and how did you overcome it?

It has been a big struggle to get an academic position – what I learnt is that I should have believed in myself more and ask more. One specific interview several years back for a fellowship in another university that was proposing something very similar to what I am doing now was very disappointing as my plan to apply single cell technologies was judged as undoable…I have kept insisting and got my academic position largely based on the application of these technologies!

6. What has been your favourite outreach activity and what made it stand out?

I am really keen in outreach activities and have done several at a broader and more focused level. It was a great experience giving a TEDx talk . The Imperial Festival is also a great opportunity to engage with the public and creative in the activities you create to explain complex science. At the same time, I love going into schools and do a very cute activity where we show how cardiomyocytes are electrically coupled using playdough, a battery with a switch, a small LED and a tone generator.

Find out more about Dr Michela Noseda's research

This month ISRMN spoke with Dr Tristan Rodriguez. 
He is a Reader in Cell and Developmental Biology at National Heart and Lung Institute.

1. What first drew you to science research and what has been your journey so far?

Probably the first thing that drew me to scientific research was a lecture while I was an undergraduate at the University of Manchester by Peter Goodfellow on the story behind the cloning of SRY, the sex determining gene. His passionate description of the process of discovery and the importance of research in different model organisms to understand complex biological problems seeded my interest in research and made me realise I would like to do a PhD. So, once I finished my degree, I was lucky enough to get accepted as an MRC student to study the genetics of fertility at the National Institute for Medical Research, that is now part of the Crick. But what really cemented my interest in science was my post-doc. After finishing my PhD, I joined the lab of the late Rosa Beddington, who was a pioneer in the field of mouse developmental biology. Her research had allowed the identification of some of the stem cell populations in the early mammalian embryo and during my post-doc I worked on trying to unravel how the first patterning events took place in the embryo. These studies served as springboard for me to be awarded a Lister Institute for Preventative Medicine fellowship to start my own group at the then MRC Clinical Science Centre, now known as the London Institute for Medical Sciences. In 2011, I was very happy to be offered a lectureship the National Heart and Lung Institute, Imperial College London, where my research group is now based as part of the Cardiac Function section. 

2. What research do you do and what do you think the impact is?

In the lab we study the mechanisms that govern cell fitness during embryonic development and how these become deregulated in disease. My background is in early mammalian development, so since my post-doc I have been fascinated with how pluripotent stem cells initiate differentiation. This process is so interesting as it involves a fundamental rewiring of the different molecular and cellular networks that govern cell identity. But importantly, differentiation occurs in the context of a developing tissue, so cells need to coordinate the process with their neighbours to ensure development occurs in a homogeneous manner. One angle we are particularly interested in is in how this coordination is maintained and we have found that one way this is done is through cell competition. During cell competition cells compare their relative fitness levels and those that are less fit than their neighbours are eliminated. So, cell competition acts as a quality control to ensure the elimination of abnormal cells and prevents them from contributing to further development or the germline. For example, work by Dr. Ana Lima, an extremely talented PhD student (now post-doc!) in the lab, recently showed that during early development cell competition eliminates cells with mutations in the mitochondrial DNA and cells that did not manage to differentiate properly (Lima et al., Nature Metabolism 2021). But cell competition is a double-edged sword, as we have also found that it can be highjacked by cancer cells to promote their growth. Dr. Katie Lawlor, another talented PhD student in the lab, demonstrated that glioblastoma stem cells use cell competition to gain an advantage over non-transformed stem cells in the stem cell niche (Lawlor et al., Genes and Development 2020). I think that these studies illustrate how we use stem cells to understand normal development, as well as to gain insights into the mechanism of disease.

3. What are your next steps? 

This is always such a hard question to answer as in so many ways it depends on what we find next! But I’ll try and give two specific answers as well as a more general one.  On the specific side, the million-dollar question of how stem cells compare their fitness levels in the different contexts of cell competition is still unresolved. By using different stem cell models where we study how stressed cells communicate with normal cells, we hope to help answer this question. Second, given the central role that mitochondria plays in cell fitness and the importance we have recently found for them in cell competition (Lima et al., Nature Metabolism 2021), we are also very interested in understanding how they modulate differentiation, as well as how dysfunctional mitochondrial dynamics contribute to heart disease. Again, we are using a combination of in vitro and in vivo systems to try and understand the different molecular, cellular and electrophysiological parts of this puzzle.  But from a broader perspective, I would like the lab to contribute to the development of synthetic stem cell-based systems for use in regenerative medicine. My role as chair of the new 3RS Hub at Imperial has helped me value the many initiatives that College wide are already happening in this direction, and I hope that our expertise in tackling how cell fitness is coordinated across a tissue will be of valuable contribution to these efforts.

4. What was your most fun or inspirational time in the lab/science?

I think it would be difficult to pick just one inspirational time in the lab/science so I will highlight two. The first was during my post-doc in the lab of Rosa Beddington. Working for someone who was uniquely talented and shaping the field of mammalian development was inspirational. But so as well were the colleagues in the lab at the time, PhD students, other postdocs and research assistants were all exceptionally good. It was exciting talking with them not only about our day-to-day work in the lab, but also about science more generally. The continuous exchange of ideas just grew my enthusiasm for science, and I now look back on that period as one that shaped the most the way I approach science now. The second time have been numerous periods since running a lab. Again, working with exceptionally good and motivated colleagues has made all the hard work feel worthwhile. Of course, there have been better times and not so good times but seeing such talented PhD students and post-docs thrive in the lab and go onto successful careers has been just so rewarding. I have also been very lucky to have in Dr. Aida I Gregorio the best research assistant I could have wished for. Aida has been the soul of the lab and made the bumpy parts of the journey worth it. So, it has been the people without doubt that have made science inspirational for me.

5. What was your biggest career or scientific disappointment and how did you overcome it?

I think that my biggest career disappointment was not being put up for tenure when I finished my Lister fellowship at the MRC Clinical Science Centre. I had been a bit slow to publish the manuscripts we had been working on in the lab and the focus of the institute had moved away from developmental biology, so when my fellowship came to an end, I was asked to look for another job. It was a very trying time, not only because of the job uncertainty this situation created but also because of the sense that I was failing those who were working in my group at the time. Looking back, I overcame this situation by a combination of luck, support from my colleagues and friends, and focussing on the essentials. The luck part was that a few weeks before my contract came to an end, I was recruited by Prof. Michael Schneider to NHLI as lecturer. But equally important was the fact that from the moment I was told that I wasn’t going to be considered for tenure, the whole group was incredibly supportive and also pulled together as one to finish the papers we had been working on. By getting these papers published we could get grants funded that supported the lab going forward. I guess that if there is one thing that this experience taught me was that failure doesn’t define who I am, it is part of science, more common than it should be, but one failure doesn’t mean that it has to be the end of the road.

6. What has been your favourite outreach activity and what made it stand out?

I found “Heart and Lung Repair Shop” organised by Professor Sara Rankin, to be the most fun and rewarding outreach activity that I have participated in. It was held at the Hammersmith Mall and what stood out for me was the possibility to reach out and communicate science to such a diverse group of people with very different social and economic backgrounds. The event was held in a small shop in the middle of the mall and consisted of a broad range of activities, from games and fun experiments to more serious small talks aimed at explaining how regenerative medicine is tackling heart and lung disease. Shoppers and other visitors to the mall would stop by the shop and participate in these activities and seeing how the majority of them engaged in such an enthusiastic way with science was extremely rewarding.

Find out more about Dr Tristan Rodriguez's research

This month ISRMN spoke with Ms Nagina Mangal. 
She is a PhD Student in Faculty of Medicine, Department of Surgery & Cancer.

1. What first drew you to science research and what has been your journey so far?

My interest in science goes back to when I was aged 6, I was wandering around my local bookshop and was drawn to a small pocketbook titled SCIENCE (I still have it by the way). As I flicked through the first couple of A5 pages I was hooked to the words and pictures, I vividly remember balancing on the bookshelf with hours passing by. At primary school, I realised that science was my greatest strength, and I particularly enjoyed physics where I became a fan of Albert Einstein. Following my secondary school and college education I became equally fascinated by the micromolecular world of science. I read for Biochemistry at undergraduate level and shortly followed this up with a research masters in Stem Cells and Developmental Biology. Upon completion I realised that I wanted to develop my scientific breadth and went on to working in world leading research groups which were great experiences and shaped my understanding and practicalities of the academic world. Prior to my doctoral studies I worked in a unique role in pancreatic cancer research where I had the privilege to engage the scientific objectives of my role directly into the clinics where I was in daily contact with patients, I knew here that I wanted to pursue a career in pancreatic cancer research. Currently, I am studying for my PhD in the Imperial Medical Cannabis research group under the supervision of Mr Mikael Sodergren, investigating the oncological role of cannabidiol (CBD) in pancreatic ductal adenocarcinoma (PDAC) in collaboration with Professor Sadanandam at the Institute of Cancer Research UK.

2. What research do you do and what do you think the impact is?

The current focus of my PhD is two-fold. I am investigating the oncological effects of Cannabidiol (CBD) (a phytocannabinoid and biological derivate of the Cannabis Sativa plant) in pancreatic cancer. As a relatively new area, its mechanism of action is not very well defined for pancreatic cancer and so I am studying the cytotoxic and immunomodulatory effects both in vitro and in vivo as a monotherapy and in combination with chemotherapy drugs. Secondly, I hope from part one of my work to focus these findings into creating a novel transferrin (TfR) aptamer tool adjoined to cannabidiol to target the cancer in patients. This area is exciting and offers a big window of exploring its therapeutic effects in many models including stem cell research.

3. What are your next steps? 

Deep down, I am an academic, so for me a post-doctoral research post is the next natural step in my career. I enjoy being in the laboratory and keeping my fingers green but also enjoy teaching and travelling around the world to meet talented people in relevant fields to network with.

4. What was your most fun or inspirational time in the lab/science?

For me, my current journey in my PhD has widened my perspective of the ups and downs that comes with being a scientist. My routine is always jam-packed, and each day brings its own set of challenges to solve. I also surround myself with positive, like-minded people who always make the day-to-day life in the lab much more enjoyable. In addition to my doctoral studies, I am also involved in teaching undergraduates enrolled in the Medical Biosciences programme. I enjoy teaching to help engage the younger minds with how amazing science truly is and enthuse the next generation of scientists. I take these teaching sessions as a break from my own world of experiments, and it gives me time to re-focus my own thoughts about my work.

5. What was your biggest career or scientific disappointment and how did you overcome it?

Disappointments/failures/rejections are always a redirection for something better. Like many other scientists I have also had my fair share of this, in particular I have learned that negative results are just as important as the positive ones.  When I go through these stages and believe me, I still do, I keep in mind that I have been at this place before and I will get through it. I find exercise and reflective thinking helps me to overcome dwelling on problems. The key ingredients for a successful career in scientific research are perseverance and hard work, as a former mentor of mine always reminded me. It is also inevitable that you will have times when things may not work your way and that’s a natural part of the process. I also reach out to people whom I look up to and trust to get their perspective on the problem as it helps me to see the problem in a way I may never have thought of. I highly recommend students during their doctoral studies to network as much as they can as it has helped me immensely.

6. What has been your favourite outreach activity and what made it stand out?

The recent pandemic issue has made it difficult for me to travel abroad to engage more with children from less developed countries to offer STEM talks. However, this is what I would like to do in the near future.  I am currently involved in a number of projects set up by the talented Dr Detina Zalli, where we engage our scientific work with cancer patients, We speak science, and where we educate the latest scientific advancements to the general public.

Find out more about Ms Nagina Mangal's research

This month ISRMN spoke with Dr Richard Wang. 
He is a Postdoctoral Research Fellow in the Department of Materials.

1. What first drew you to science research and what has been your journey so far?

I consider myself an engineer but have always recognised the synergy between the scientific understanding of ‘why’ and the engineering understanding of ‘how’. I first experienced scientific research during my undergraduate studies at the University of Sydney through the Talented Students Programme, where I joined Prof. Jan Marc’s group outside of my classes to study the effects of turgidity on plant cell development and cortical microtubule orientation. As I progressed through my undergraduate studies, I began to take more interest in biomedical engineering, and pursued my Honours research studying the immunogenic effects of polymeric skin grafts post in vivo implantation.

After completing my undergraduate studies, I explored my options in industry and worked at ResMed, where I transitioned through various teams developing sleep apnoea and portable life support systems. However, the allure of cutting-edge research drew me back to the University of Sydney, where I commenced a PhD programme in Prof. Anthony Weiss’ group. It was during my PhD that I began to shape my career interests and hone my skillset for biomedical and tissue engineering. My thesis focussed on vascular engineering using 3D printed ice and elastin-based biomaterials; a multidisciplinary project that allowed me to develop many of the skills and ideas behind my work today. During my PhD, I also became interested in electronics and co-founded a start-up that developed low-power long-range miniaturised asset tracking devices, which was successfully acquired by a multibillion-dollar investment group. Towards the end of my PhD, I was incredibly fortunate to be awarded a Rosetrees Fellowship with the opportunity to work at Imperial in the wonderful group of Prof. Molly Stevens along with synergistic collaborations with Prof. Nicholas Peters and Prof. Sian Harding. These opportunities have provided me with diverse experiences and imprinted on me the importance of bringing together various skillsets to tackle the multidisciplinary challenges inherent to regenerative medicine.

2. What research do you do and what do you think the impact is?

I’m particularly interested in bioelectronics, which is a field that uses artificial intelligence and electronics devices to measure and harness biological processes and direct cell behaviour. My current work focusses on cardiac bioelectronics, which forms the interface between electronics and cardiac tissue engineering. By using miniaturised electronics devices in the context of cardiac tissue engineering, we aim to establish a new generation of personalised healthcare solutions that can provide superior diagnostics for improved clinical results in heart failure patients. Stem cells are one of the fundamental pillars supporting this multidisciplinary research. I’m especially fascinated by the ability of induced pluripotent stem cells (iPSCs) to differentiate into numerous cell types. They are particularly important in my work as cardiac tissues have poor regenerative capabilities – thus, the ability of iPSCs to differentiate into cardiomyocyte-like cells provides a sustainable source of cells we can use along the long and arduous journey towards clinical translation.

3. What are your next steps?

As an early-career researcher, I’m still very much in the honeymoon period of research where the days are filled with exploring exciting new ideas and pure creation. I wish to enjoy this time and continue establishing myself as a leader in this field by pushing the boundaries of my research and cultivating my relationships with the many talented people I work with. In particular, I hope to explore more innovative, high-risk, high-reward research during these years as an early-career researcher, so that I may elevate my credibility, recognition, and influence in the field.

4. What was your most fun or inspirational time in the lab/science?

The most important lesson I’ve learned is to make your day-job fun. For me, the most fun and inspiring times are when I work with great people in the lab. Whether it be pushing through the night to meet a project milestone, scribbling down an exciting new design on a napkin over lunch, or having a beer after work to lament and commiserate over failed experiments, the comradery that comes from working together with ambitious, talented, and driven people is what makes it all worth it!

5. What was your biggest career or scientific disappointment and how did you overcome it?

I’ve had so many disappointments over the years that I’ve learned to no longer dwell on them. Growing a thick skin in the face of failure is something every researcher must have in order to survive in science. I try to categorise and deal with my scientific disappointments and career disappointments separately. For the former, I always remember the words a close friend once said to me, which is “the world’s toughest problems are solved by people no smarter than you and I.” For the latter, I took the advice from a previous mentor and keep a folder on my computer filled with emails of successful manuscripts, fellowships, and awards, and I look through them every now and them when things get tough. 

6. What has been your favourite outreach activity and what made it stand out?

Hard work and good results are only part of the job – I think this concept still eludes many of the most talented researchers today. During my PhD, I was part of the in-house Early-Mid Career Researchers Committee where we developed an initiative to promote networking between scientific researchers and industry partners representing various sectors ranging from NGOs, financial services, consulting, and even start-up venture capitalists. The most striking impression I received through the event was how narrow the field of science is in relation to the rest of industry, corporations, and communities. As researchers, we tend to put on our blinkers and immerse ourselves in our work, making it very easy to develop a skewed perspective of where we fit in to the bigger picture. The initiative highlighted the necessity of outreach for bilateral education; to firstly communicate our work to non-researchers, but to also remind ourselves that science is still one piece of a much larger puzzle.

Find out more about Dr Richard Wang's research

This month ISRMN spoke with Dr Koralia Paschalaki. 
She is a Postdoctoral Clinical Research Fellow in the Vascular Section, National Lung and Heart Institute.

1. What first drew you to science research and what has been your journey so far?

I qualified in Medicine from the University of Crete (Greece) and then completed specialist medical training in Respiratory Medicine in Athens. My interest in clinical research developed during my speciality clinical training. I decided to pursue a PhD and I joined Professor Vassilis Gorgoulis’ group (University of Athens), who is an internationally known scientist working on cancer and cellular senescence.

After completing my clinical training, I was awarded a competitive fellowship from the Hellenic Thoracic Society. With this fellowship, I joined Professor Peter Barnes’ group at Imperial College London, internationally known for his vast contribution to the understanding of asthma and COPD pathways and the development of treatments. This was a life changing experience. I was inspired by the depth of knowledge on complex molecular pathways and enthusiasm for research and was encouraged to work on a basic science project investigating endothelial progenitors’ dysfunction and relevance to cardiovascular comorbidities in patients with COPD.

This is how I started my basic science research journey and I joined Professor Anna Randi’s group, who leads on studies on endothelial biology and vascular homeostasis. I learned a wide variety of laboratory techniques and invested a lot of time to optimise a challenging method of isolation of endothelial progenitors from peripheral blood named endothelial colony forming cells (ECFC, or blood outgrowth endothelial cells). We now have an effective protocol to isolate and study this rare cell population.

Having the opportunity to work within three departments with different scientific interests (Airway Disease and Vascular Science in Imperial College and Histology Department of University of Athens), I have studied different aspects of basic science and developed my own scientific questions and scientific niche. In my PhD, I have demonstrated for the first time accelerated ageing in endothelial progenitors from smokers and COPD patients due to epigenetic molecular dysfunction. This work, published in ‘Stem Cells’ has been highly cited, and I have received positive feedback with many invitations as a speaker and 7 prizes and travel fellowships between 2011 and 2013 from both the Respiratory and Cardiovascular Medical Societies, a very gratifying experience for me.

I have been very fortunate to collaborate with exceptional clinicians and basic scientists and advance my skills in both areas within NHLI. It has been such a pleasure to work clinically within the Interstitial Lung Disease Unit with Professor Athol Wells, and enjoy investigating complex clinical cases with a multidisciplinary team. It is stimulating to form questions in clinic and trying to set up appropriate methods to study them in the laboratory and the other way around.

It has been very rewarding after many years of hard work, when I was awarded a British Heart Foundation (BHF) project grant to start my own research group.

2. What research do you do and what do you think the impact is?

My aim is to characterize the pathways involved in endothelial senescence and vascular dysfunction in patients with chronic lung disease. I study endothelial function by isolating endothelial precursors from peripheral blood, known as endothelial colony forming cells. This is a challenging method that few groups undertake worldwide, and I have developed significant expertise on that field. This rare cell population gives us the unique opportunity to perform molecular studies of endothelium with patients’ samples in a non-invasive way, but also explore possibilities to use them for personalised medicine and regenerative studies. In my studies, I use traditional cell cultures but also novel 3D models. I am developing a tissue engineering blood vessel model of vascular ageing using patients’ cells for molecular studies and drug screening purposes.

I am one of the few respiratory researchers that work closely with vascular experts and try to underpin the cardiovascular comorbidities in patients with chronic lung disease, such as COPD and pulmonary fibrosis. I hope that by doing combined molecular and clinical studies, to be able to early identify patients with increased risk to develop cardiovascular disease for prompt treatment which can modify disease development and possibly improve outcome of disease.

3. What are your next steps?

Certainly, the current pandemic crisis has created significant challenges for clinical studies, however we have started recruitment of patients and I am very excited about that. I am currently developing my research team and recruiting research staff to work along-side me on my project, a new experience for me. I am working on two manuscripts and my aim is to apply for a Clinical Research Fellowship, to expand my research activities and further develop myself as a clinician scientist.

4. What was your most fun or inspirational time in the lab/ science?

I can certainly recall cases of me working in the lab during my PhD that after a lot of hard work and negative results you get some interesting and unexpected findings that make you think on a different way on your project and develop new ideas. For example, it was gratifying when after many functional in vitro assays using ECFC, I found that endothelial cells from smokers and COPD patients were prematurely aged compared to healthy non-smokers. This helped me to start building my own research ideas, testing new hypothesis and build gradually the current research area of my interest.  

The existing challenges due to the pandemic have imposed many difficulties on our research projects, but on the other hand have motivated us to explore new ideas and avenues of using our research expertise. It is stimulating when we all work together, exchange ideas and try to set up new collaborations and research projects to tackle a common threat. I have the pleasure to interact and work both as a clinician and as a researcher on new projects on COVID-19, which is very exciting!

5. What was your biggest career or scientific disappointment and how did you overcome it?

As most of us in research, there have been disappointing times related to a rejection of a manuscript or a grant / fellowship application. I have now realised that this is part of the process, you get the feedback, you work on that and you come back stronger and more confident!

6. What has been your favourite outreach activity and what made it stand out?

It has been always difficult to find time to devote to outreach activities, but it is something so useful and rewarding for what we do. I have been involved in activities within Professor Randi’s group at Imperial Festival, knitting vessels with my colleagues and discuss with non-scientific audience about the importance of the vascular system. Over the years, it has been always interesting to have undergraduate and postgraduate students visiting our lab and discussing on career pathways related to research. It has been very helpful, when for my recent application to Ethics Committee, I discussed my project with patients with COPD and had very useful feedback on the design of the study and patient information sheet and consent form. It is amazing how much valuable advice you can get form active patients involved in clinical research!   

Find out more about Dr Koralia Paschalaki’s research

This month ISRMN spoke with Dr Chiu Fan Lee. 
He is a Senior Lecturer in the Department of Bioengineering.

1. What first drew you to science research and what has been your journey so far?

I was not academically inclined until I started the International Baccalaureate (IB) programme at Champlain College Saint-Lambert in Montreal. I was particularly inspired by my Theory of Knowledge teacher Dr Steve Hreha, who made me appreciate the wonder of intellectual pursuit. After IB, I did a Joint BSc in Mathematics and Physics at McGill University. At that time, I was more interested in mathematics than physics and I did my honours thesis on number theory. After McGill, my mathematics interest led me to pursue the well-known one-year Part III mathematics course at the University of Cambridge. During that time, my interest gradually shifted to physics. After Cambridge, I started a DPhil in quantum information theory at the University of Oxford. Towards the end of my DPhil, I was very fortunate to be awarded a junior research fellowship at University College, Oxford, and then another independent fellowship afterwards. The independence enabled me to explore other fields beyond quantum physics, which quickly led to my realisation that biological physics is my true calling.

I think I was very lucky to have the time and opportunity to try out various fields, and to interact with researchers in diverse disciplines. These experiences certainly served me very well in the many scientific challenges I now face since biological physics is an extremely multi-facetted field that requires researchers to be equipped with a wide range of tools.

2. What research do you do and what do you think the impact is?

As a modeller why are you interested in stem cells? I run a theory-driven biological physics group. In other words, my group aims to answer biological questions for which theoretical inputs are indispensable. The impact of our work usually lies on the development of new theoretical formulation and understanding that enable us to explain a biological phenomenon and to make testable predictions.

Regarding stem-cell research, my collaboration with Prof Cristina Lo Celso’s group started almost five years ago, and I have always been mesmerised by the images and cell tracking data that Cristina’s group obtained in the murine bone marrow environment. The complexity of the haematopoiesis also fascinates me. I think the diversity of cell types involved, the temporal interplay of cell cycles and cell differentiations, and the intriguing regulatory network render this biological system perfect for, and also in need of, a statistical physics approach to unravel its secrets.

3. What are your next steps?

I believe that as biology becomes more and more quantitative, biophysicists will become more integral to the discovery process. Ultimately, any “mechanism” that biologists speak of is fundamentally a toy model of the underlying biological process, and physicists can play a crucial role in making sure that these toy models are physically correct and quantitatively plausible. In fact, there are two great recent examples of biology and physics flourishing together: one is morphogenesis / cell tissue dynamics, whose study relies crucially on active matter physics; the other is cellular phase separation, whose rapid development would not have been possible without the accompanying understanding of the physics of phase separation.

While some of the best life sciences centres in the world realised that biology and physics need to go hand in hand, this is still not widely acknowledged everywhere. Revealing this synergy is a key motivation behind the Physics of Life Network of Excellence set up two years ago that is headed by Robert Endres (Life Sciences), with Chris Dunsby (Physics) and me as co-Directors. We aim to use this platform to spread the news that the most exciting area of life sciences and physics at the moment is at their interface, where new knowledge in both biology and physics will be generated.

Scientifically, a key next step for me is to develop the next-generation methodology to facilitate theoreticians to uncover universal features in biology, based for example on renormalisation group methods. While physicists are familiar with the notion that quantitative predictions are possible with minimal empirical inputs, this approach remains relatively unknown in life sciences. Interestingly, the intellectual lineage of this approach can be traced back to the law of large numbers in statistics, which of course underlies the quantitative nature of all experimental sciences.

 4. What was your most fun or inspirational time in the lab/science?

I think it is very hard for me to pinpoint one particular example, but I recently came across an article called “Thirteen tips for engaging with physicists, as told by a biologist”, and tip 13 is “Physicists laugh a lot”. This really rang a bell for me. One reason for this observation could be that physicists are trained to seek connections in different systems, we therefore are apt to find common themes among superficially distinct systems. And when you see the connection, you can’t help but be humoured by the comic twist of nature. One recent example from my work is the connection between the dynamics of planar cell tissues and how the edge of a piece of paper catches fire – both systems can follow the same long-time dynamics as dictated by the so-called Kardar-Parisi-Zhang equation. This work was done in collaboration with John Toner (Oregon) and Leiming Chen (China University of Mining and Technology) a few years ago. Indeed, whenever we come to discuss together (which is not very often given the geographical and time zone separations), it is always laugh-out loud fun for me. In some sense, I would like to think that engaging in a scientific discussion is like playing in a jazz band (not that I am good enough a musician to play in any jazz band) – we improvise with our “what if…” and “how about…” caricature of the world, and build upon each other’s ideas in turn. The other great thing about this is that, just like being a musician, it gets more fun as you learn more, know more, and are more experienced. So, I think my fun time in science will only get better and better.

5. What was your biggest career or scientific disappointment and how did you overcome it?

Almost all academics will say that our job comes with regular and perhaps constant disappointment, since having grants and papers rejected is likely to be the norm rather than the exception. But if I had to pick one great disappointment, I would say it was when my fellowship in Oxford was ending and I did not manage to get the fellowship I wanted to stay in the UK and had to move to Germany instead. It was difficult for me because my then girlfriend (now my wife and mother of our two children) was doing her DPhil at Oxford. Although it was not easy for me personally, it turned out to be a blessing in disguise scientifically since the Max Planck Institute for the Physics of Complex Systems in Dresden that I moved to was, and still is, one of the best places in the world in biological physics. My stay there definitely helped me significantly in shaping my own outlook and approach to biological physics.

 6. What has been your favourite outreach activity and what made it stand out?

I was the Director of Outreach of Centre for Doctoral Training in Fluid Dynamics across Scales and I helped organise engagement activities at several Imperial Festivals and later the Great Exhibition Road Festivals. What I always found most rewarding is to see the amazement and excitement in the eyes of children when they tried out the hands-on activities. My family always came along, and I know first-hand how much my son enjoys these festivals.

Find out more about Dr Chiu Fan Lee’s research

This month ISRMN spoke with Dr Floriane S. Tissot. 
She is a Research Associate in the Department of Life Sciences.

1. What first drew you to science research and what has been your journey so far?

As many scientists, I have always been curious to discover new things as well as very enthusiastic to set up the methods leading me to these discoveries. Hence, I naturally turned to scientific studies. The first years studying biology at the University of Nice Sophia-Antipolis (France) made me realise that doing a PhD and becoming a researcher will be the ideal job for me. After 4 years of theoretical classes, I finally performed my first experiments in a lab and these 6 months of internship gave me a quick overview of what the job of a scientist can be, with all the ups and downs that working at the frontier between what is known and what is not known yet involve, and I enjoyed it. Thus, after my master’s degree, I started a PhD in Chloé Féral’s lab at the Institute for Research on Cancer and Aging, Nice. During my 4 years of PhD, I studied the role of a transmembrane protein, partners of integrins, CD98hc in the interaction between dermis and epidermis during skin aging. I also had the chance to develop side projects including one on the functional transfer of transmembrane protein via small extracellular vesicles and its role in wound healing. As the previous ones, this experience comforted my choice of working in research, hence the next step was to look for a postdoc. I wanted to go abroad and continue to work on the interaction between different cellular compartments. During a chat about my future career steps, a friend advised me to have a look into Prof Lo Celso’s work. I liked her broad and integrated vision of biological systems from physiology to pathology associated with  powerful technique such as mouse bone marrow intravital microscopy and collaborations with different scientific fields such as mathematic modelling. Hence, I decided to contact her to do my postdoc in her lab. I am now working in her lab at Imperial College London since October 2018 and I truly enjoy it.

2. What research do you do and what do you think the impact is?

Haematopoiesis is the process during which blood and immune cells are formed from haematopoietic stem cells. Normal steady-state haematopoiesis takes place in the bone marrow microenvironment (BMM). Under pathological conditions such as acute myeloid leukaemia (AML), the BMM is hijacked by malignant cells and switch toward being leukaemia permissive environment. AML is an aggressive leukaemia with a cure rate of only 5-15% in patients older than 60 years old. The general therapeutic strategy has not changed substantially in the last 30 years. Therefore, new therapeutic approaches need to be developed. Thus, it is critical to understand how AML cells outcompete healthy haematopoiesis and generate an environment supportive of leukemic cells. The biomechanical properties of cell’s microenvironment have been shown to be important regulators of cellular behaviour during tissue homeostasis as well as tumour progression. However, little is known about the BMM biomechanical properties during leukaemia progression and its impact on healthy haematopoiesis. My project aims to understand how AML cells impact the mechanical properties of the bone marrow and its impact on healthy haematopoiesis. In addition to intravital microscopy this work leads me to develop new skills and techniques in particular in histology and image processing and analysis. I thus discover the world of programming and its powerful applications in data analysis, and I am really keen to progress in this new skill.

3. What are your next steps?

 My next steps will be to finish and publish the different projects that I started in Cristina’s lab. After that, I would love to stay in academia and continue to do research.

4. What was your most fun or inspirational time in the lab?

What is really nice about research is that we are working at the edge of the known and the unknown. As a consequence, every day of work can lead to a new discovery, usually a small one but by adding up all the small ones we can create an all-new story that contribute to the general knowledge. To me this is one of the great privileges that our work brings us.

5. What was your biggest career or scientific disappointment and how did you overcome it?

I can’t remember one specific scientific disappointment. developing a research project comes with a lot of good and inspiring moments but also its share of period of doubts and failure. I am passionate about my work and it is sometimes difficult for me to take some perspective, specially during the down moments. In that case, talking about it to my colleagues and/or friends helps me to find this perspective and the strength to bounce back and go back on track.

6. What has been your favourite outreach activity and what made it stand out?

I have never been very comfortable to talk in public. To try to overcome this, during my PhD, I participated to a national contest called “My PhD in 180 seconds” where the aim is to explain your work to a lay audience in 3 minutes. I really enjoyed this experience at all levels. I found very interesting to find how to explain my work in non-scientific words while going into details. Then this had to fit in the allowed time which due to its short duration requires to speak in a clear and intelligible way. Overall, this was a really good exercise that participates to fulfil its first aim to help me with public talks but also made me realize that I really like to make the science available to a lay public and to exchange with them about it. Hence, following this, I participated to several science festivals open to children and lay audience.

Find out more about Dr Floriane S. Tissot’s research

This month ISRMN spoke with Dr James Armstrong.

1. What first drew you to science research and what has been your journey so far?

I’ve always been curious about the way things work and coming up with inventive solutions when things don’t work. So studying science was always a natural fit for me and I now know that academia is the only job I want to do for the rest of my life. But I wasn’t always so sure about this and the route I took to my current research wasn’t at all linear or planned. I studied chemistry for my Master’s degree because I love the theoretical side: how almost everything in the world can be understood and described by chemical bonds and thermodynamics. But I really didn’t enjoy the practical side of chemistry: long days in a hot lab making disappointingly small quantities of powder was not for me. The turning point for me was an amazing opportunity to do an undergraduate lab placement at the University of Tasmania. I worked for three months with a brilliant team led by Prof. Rosalind Guijt building microfluidic devices for contactless chemical sensing. This completely opened my eyes up to the possibilities of science beyond the synthesis lab.

I then stumbled upon a great opportunity at the Bristol Centre for Functional Nanomaterials, a doctoral training centre at the University of Bristol. Here, I was able to do rotations for one year in several different labs, and got the chance to work with physicists, engineers, and chemists exploring the world of nano: liquid crystals, atomic force microscopy, small-angle x-ray scattering, electron microscopy... This programme also gave me the opportunity to do a PhD project with Prof. Adam Perriman, Prof. Anthony Hollander, Prof Steve Mann, and others – an amazing mentorship team with a really exciting project looking to oxygenate stem cells for cartilage tissue engineering. Through the doctoral training centre network, I also met PhD students working on magnetism and acoustic physics: which sparked the ideas that are behind my research today! Since graduating with my PhD, I’ve been fortunate to have been continuously supported by fellowship awards from Arthritis Research UK and the MRC. This gave me the opportunity to work in the incredible group of Prof. Molly Stevens but also the independence to pursue these ideas in my own direction.

2. What research do you do and what do you think the impact is?

I consider myself to be a tissue engineer: I use different combinations of cells, biomaterials, and growth factors to grow cartilage, bone, muscle, and other types of tissue. The ultimate goal is to build tissues that can be used as clinical grafts to treat patients with damaged or diseased tissues (e.g., those with osteoarthritis) or applied as a model system to study how tissues develop, become diseased, or respond to drug treatment. But in order to engineer translational tissue grafts and biologically-relevant tissue models, we need to develop ways to replicate the natural structure of tissues, such as the cell and matrix alignment, different tissue zones, vasculature, etc. It is unlikely that we will be able to exactly replicate the end result of millions of years of evolution, but what we do have is the benefit of human ingenuity and the opportunity to use technologies to control the assembly and growth of our engineered tissues.

One of my main areas of research has been the development of a method for using ultrasound standing waves to remotely align cells for skeletal muscle engineering. I’ve also been developing different ways of programming biomaterials with growth factor gradients to grow the cartilage-bone interface. I am also a big fan of the possibilities of 3D bioprinting in building complex tissues and have been fortunate to work with some great scientists in the Stevens group helping to develop new approaches for printing tissue vasculature. While we still have a long way to go before these systems are used clinically, I believe that these and , will be essential for the field to truly realize the translational impact of tissue engineering. You can find out more about my research on my professional website.

3. What are your next steps?

I want to stay in academia and couldn’t imagine what I would do otherwise! I have lots of ideas for how to branch these technologies out into other areas of regenerative medicine and cannot wait to set up and grow my research group. I’ve applied for a Future Leaders Fellowship and am also on the academic job market, something that has been particularly challenging with the pandemic! For now, I am enjoying my time finishing off and writing up my remaining projects at Imperial.

4. What was your most fun or inspirational time in the lab?

My time as an Assistant Supervisor at Imperial has been incredible. I love working with the diverse group of PhD students at Imperial and helping them develop into independent, critical-thinking scientists. Their enthusiasm and intelligence are truly inspirational (and keeps me on my on my toes) and it is a joy for me to see them give a fantastic conference presentation, pass their viva, or just overcome a difficult experiment in the lab. The students at Imperial are among the best in the world and I have learned so much from them. Hopefully, they have learned something from me too!

There is also a serious side to this – I know from experience the emotional peaks and troughs of science and the mental toll of doing a PhD. I try to always be available to any student that is struggling with mental health or wellbeing during their studies. I’m sure that I haven’t always got it correct, but I do hope that over the years I have been able to offer the appropriate pastoral support. I do know that my students are among the best friends that I have made at Imperial and I hope to stay in touch with them all after our time at Imperial.

5. What was your biggest career or scientific disappointment and how did you overcome it?

I definitely had a major case of the second-year blues in my PhD when nothing in the lab was working and I developed doubts about the methods and impact of my work. I started to privately doubt whether I was cut out for science and started to consider alternative careers. But this was where my supervisory team were superstars. They were extremely quick to identify that I had concerns, and they spent a lot of time helping me work through the problems. My primary supervisor, Prof. Adam Perriman, has always looked out for me, even now, and I am very grateful for all his time and support!

6. What has been your favourite outreach activity and what made it stand out?

After we locked down in Spring 2020, I contacted a friend of mine in the States (Dr. Brian Aguado, new PI at UCSD) with the idea of setting up a series of online science webinars. These events are very commonplace now, but we were among the first to set up such an initiative. Given the widespread cancellation of conferences in 2020, we wanted to provide a public, open-access forum for early career researchers to present their exciting science. Within two weeks, Virtual Seminars in Biomedical Science was born!

We originally set up one month of speakers but we received so much incredible feedback from attendees that we decided to keep on going with talks almost every week (my co-organizer is now Dr. Natalie Kirkland, also UCSD). We now have over 1200 registrants and have been fortunate to host speakers from the very best institutions in the world – MIT, Harvard, Stanford, Cambridge, and of course Imperial! I was struck by how this format of seminars is a truly democratic form of dissemination - we have attendees from all over the world, many of which would not have had the access to the quality of speakers that we have been fortunate to host. It makes me realize how privileged I am to work at an institution such as Imperial and has made me determined to continue this series for as long as there is interest.

Find out more about Dr James Armstrong’s research

This month ISRMN spoke with Dr Sílvia Ferreira.

1. What first drew you to science research and what has been your journey so far?

I am a biomedical engineer with a background in pharmaceutical sciences (MSci 2007, MRes 2011, University of Porto, Portugal), nanomedicine (PhD 2012, University of Minho, Portugal) and tissue engineering. After training in pharmacy, pharmaceutical industry, water and food analysis, clinical analysis and forensic toxicology laboratories, I did my ERASMUS at UCL and I realized I loved multidisciplinary research and that science was what excited me. During my PhD, I developed nanogels that target antigen-presenting cells to be used as vaccine delivery systems for antigens and adjuvants to prevent and treat cancer. Then I moved to KCL where I focused on studying how the 3D microenvironment impacts stem cell behaviour and drives differentiation or quiescence. In 2018, I joined ICL and have assessed the potential of 3D-printed hybrid scaffolds to drive chondrogenesis in vitro and have evaluated their biosafety and inflammatory response in vivo. I have started my Wellcome Trust ISSF Springboard Fellowship in November 2019 at Inflammation, Repair and Development Department, at National Heart and Lung Institute.

2. What research do you do and what do you think the impact is?

I like to study cell-material interactions and how the biomaterials physical properties impact stem cell behaviour and the inflammatory response in the context of tissue engineering to improve tissue regeneration. I like to conceive new scientific ideas and to design new experiments to answer interdisciplinary questions collaborating with different experts. I like to bridge complex problems facilitating the linkage between bioengineering, biology, immunology, biomaterials to ultimately solve clinical needs developing strategies to treat patients.

3. What are your next steps?

I want to become an academic and I am applying for Fellowships. I want to understand the mechanisms of immune-stem cell crosstalk and how to modulate the regenerative outcome of musculoskeletal diseases or injuries using biomaterials

4. What was your most fun or inspirational time in the lab?

Presenting and discussing my work at multidisciplinary meetings, namely Gordon conferences, inspire me and energise me to develop new scientific questions.

My ‘Human Stem Cell' image received the Wellcome Trust, MIT Koch Institute and Nature Image Awards in 2016. The image was exhibited in the London Science Museum and other museums and galleries in more than 70 countries and was described as ‘mesmerizing’ after the press release. I was contacted globally by several journalists from different agencies, artists, students and got invited to ‘tell the story of the image’ in numerous events. The image was selected third best of the Wellcome Collection by the general public and was recognised by Nature in the publication entitled: ‘366 days: the year in Science, Images of the year by Nature’s art design team’.

5. What was your biggest career or scientific disappointment and how did you overcome it?

As any scientist, I learned from my multiple failures and rejections and became more resilient and tenacious. I developed my support system and my network. I always pushed positive thoughts, worked hard and smart, and focused on the main goal. I tried to update myself, attend courses and have had great mentors and coaches throughout my career.

6. What has been your favourite outreach activity and what made it stand out?

I have always advocated and volunteered for outreach and public engagement activities. Recently, I participated in Pint of Science, Native Scientist, Bring Your Child to Work Day and International Day of Girls and Women in Science. These activities not only help me to disseminate the value and impact of my research but also allow me to inspire school kids about STEM and to develop their curiosity and creativity.

Find out more about Dr Silvia A. Ferreira’s research

This month ISRMN spoke with Dr Ioanna Mylonaki.

1. What first drew you to science research and what has been your journey so far?

I had always been driven from innate curiosity to understand systems around me. My love for discovery, initially drove me to study pharmaceutical science at the University of Athens, Greece. Later I realised I could join a community of researchers eager to bring scientific discovery to patients and improve their life quality. That is when I decided to do a PhD in pharmaceutical technology at the University of Geneva, Switzerland. I developed a perivascular formulation for the prevention of intimal hyperplasia following vascular by-pass surgery. I was given the opportunity to join a project from its naissance; and perform the formulation development, the in vitro studies and latter test it on two animal models. The most intriguing part of this project is that it was driven by a need of clinicians, who provided their clinical expertise to develop a product that would really benefit patients undergoing bypass surgeries. This project has taken the route of becoming a spin-off company of the University of Geneva and is currently expanded in its business perspective to secure funding that would allow for its testing in a clinical setting.

2. What research do you do and what do you think the impact is?

I am currently a postdoc fellow of the Swiss National Science Foundation, at the bioengineering department of Imperial College London, working at the group of Molly Stevens. My scientific interests revolve around the efficient delivery of small molecules, genes and cells for Advanced Therapies (gene and cell therapies). I am fascinated by the recent advancements on cell and gene therapy and intrigued by the bottlenecks of how to deliver such entities. Indeed, despite the major advancements of pharmaceutical research towards biological therapeutics, little has been achieved for the delivery of these systems. I am set to transpose the observations that biologists make in a cell culture environment to the complexity of in vivo systems where toxicity, distribution, immune response, pharmacokinetics/pharmacodynamics can become important barriers for the success of the therapy.

3. What are your next steps?

For the next few years, I aim at developing systems for the delivery of cells in the heart, that would induce cardiac regeneration following myocardial infraction. I want to bridge the gap between biological research, biomaterials and clinical application to bring safe and efficient solutions for cardiovascular regeneration. I intend to fully embrace the ‘luxury’ of being in an academic environment, that allows for blue-skies research and exploration of high-risk-high-reward research. And especially for translational academic researchers that cannot compete with the resources of big pharma, it is crucial to explore innovation routes that are too risky for the industry.

I also intend to dive into the entrepreneurial ecosystem and understand ways to translate positive scientific outcomes to efficient Advanced Therapies. Very often, scientists focus in their lab work and fail to apprehend the bigger picture of scientific research. I would like to deeply understand what the unsolved medical conditions are, what needs to be improved in the patients, and most importantly what are the economic extensions behind this that would allow for the necessary research expenditure.

4. What was your most fun or inspirational time in the lab?

By the end of my PhD I had to analyse hundreds of histological slides of different organs and several stainings. We had designed a blinded-experimentin which not me nor my colleagues knew what condition we were testing. We were working for months on the in vivo study and later it took us several weeks to analyse the slides. Once all the data was analysed, we were finally able to reveal the groups. It was a great relief and joy to find out that our scientific assumption was proved. It really made me feel that the effort was worth it.

5. What was your biggest career or scientific disappointment and how did you overcome it?

My biggest scientific disappointment came when I realised how much irreproducible research is being published. Even in very high impact factor journals! I was in shock when I read the famous Amgen study citing that only 11% of scientific findings were confirmed, out of 53 preclinical cancer papers analysed (Nature 483, 2012).  And this is translated in $28b a year spent on irreproducible biomedical research (PLOS biology, 13-6, 2015). Ever since I am particularly meticulous when describing my experiment protocols and incite my students to do the same. I have also engaged to efforts such as protocols.io or experoment.com that aim to increase research reproducibility.

6. What has been your favourite outreach activity and what made it stand out

I was once invited to give an interview at the Swiss press on the outcome of my research. It was great fun to express very complex concepts in simple language for the wide audience. I obviously shared the communication with friends and family. Interestingly, their feedback made me realize that the society does not fully apprehend the importance of scientific research. This encouraged me to get involved in a growing number of outreach activities and consider the time spent on this truly imperative.

This month ISRMN spoke with Dr Kirsten McEwen. Find out more about research in Kirsten's lab here.

1)    What was your journey through science so far?

It started with one genetics class in high school that captured me. Although I didn’t take biology in my final school years and instead focused on maths, chemistry and physics, I took a gamble and did a Biomedical Science Bachelors. It paid off, I love molecular biology and was awarded a scholarship to undertake my PhD with Anne Ferguson-Smith at the University of Cambridge. Here I took my first step integrating experimental and computational approaches and discovered an epigenetic signature of genomic imprinting. During my post-doc with Petra Hajkova at the MRC London Institute of Medical Sciences I expanded beyond imprinting to look at epigenetics and gene regulation more globally. I was next awarded the Imperial College Research Fellowship to build my own research programme.

2)    What research do you do and what do you think the impact is?

My research programme has a core focus on cellular heterogeneity, which is emerging as a key determinant of health and disease. We know that all cells are not equal: diversity exists even between cells of a single cell type. The proposed functions of heterogeneity are broad and include controlling cell fate decisions, disease risk, cancer metastasis and drug resistance. Very little is actually understood regarding these processes and my goal is to identify the mechanisms and consequences of heterogeneity to ultimately learn how to improve disease outcomes.

Recent work identifies drivers of heterogeneity in pluripotent stem cells with potential implications for cancer. We show that kinase inhibitors – which are currently in clinical use to treat various cancer types – can induce heterogeneity. This may increase the risk of drug resistance and metastasis so we’re now testing if this does indeed happen in cancer cells, an exciting step toward more translational research.

 3)    What are your next steps?

Immediate next steps are to get the reviews finished for two papers I’ve just submitted (check them out on BioRxiv). I have two other projects I’m hoping to submit before I’m off for maternity leave, then I’ll be learning how to balance motherhood and an academic career!

4)    What was your most fun or inspirational time in the lab/science?

The opportunity to direct my own research programme has been incredibly fun, inspirational and rewarding for me. Coming up with fresh ideas and testing these out is what drives me. I also really enjoy supervising and seeing my team members develop towards becoming independent scientists.

5)    What was your biggest career or scientific disappointment and how did you overcome it?

I’m passionate about my work, which means I take both the ups and downs very personally. Coping with disappointments – and in academia these are many and varied – is essential. I remind myself to keep some perspective, get advice from many sources and appreciate what you learn at each step.

6)    Have you participated of any outreach or public engagement activities recently?

I was selected for a Rising Stars public communication course during my PhD which gave me invaluable tools and experience. Since then I’ve participated in science festivals and museum exhibitions, given outreach seminars, undertaken Wikipedia edit-a-thons and been interviewed about the implications of stem cell research.

7)    If you were to go back and start your PhD over again, what advice would you give yourself?

Network. I’m shy at heart and it has taken time to build up my networking skills. Remember that scientists are curious and most genuinely want to hear about your research. Learn how to advocate for yourself, ask for help when you need it and if you spot a potential collaboration, get in touch to discuss opportunities.

This month ISRMN caught up with Dr Claire Higgins. Find out more about research in Claire's lab here.

1)    What was your journey through science so far?

For my undergraduate degree I studied Natural Science at Durham University in the UK.  There was no research project associated with this and so I got a summer job as a research technician at the Sanger Institute.  I quickly realised that I enjoyed working in a laboratory, and hence I applied for a PhD in the lab of my favourite lecturer.  When I was partaking in my PhD I still hadn’t quite figured out my ‘career plan’ but a natural next step was to do a postdoc.  I only applied in the USA as I wanted to experience a different research culture, and moved to Columbia University in New York in December 2007 to take up a position there.  I went initially for a 2 year stint, but about a year in I realised that I definitely wanted a career in academia.  I therefore starting applying for fellowships, and received one which gave me funding and kept me in my postdoctoral research lab for 6 years.  After this, I applied for faculty positions throughout Europe and thankfully got a position in the Department of Bioengineering at Imperial.  I joined the faculty here as a Lecturer in 2014.

2)    What research do you do and what do you think the impact is?

My lab works on tissue regeneration, using human skin and hair follicles as a model system.  We try to regenerate skin after injury, specifically traumatic injury, so it is appropriate for its new function.  For example, with skin repair you get a scar which is devoid of follicles, nerves and blood vessels.  Essentially it is a living bandage but not a functional tissue.  We work with the belief that initiating hair follicle growth in scar tissue will spur on the recreation of developmental processes, and in turn promote angiogenesis, neurogenesis, and reestablishment of a functional skin.  Likewise, sometimes skin does regenerate but it is no longer suitable for its new function.  An example here would be skin on the residual limb of an amputee…it covers the limb which is all well and good, but it cannot bear load as efficiently as foot skin, and will ulcerate when patients try to walk with a prosthesis attached.

 3)    What are your next steps?

My lab mainly works with human tissue with the end goal of having translational research.  Currently, I am applying for funding to initiate a cell therapy trial to reprogramme skin on an amputated limb to become load bearing. It is a huge career aspiration of mine to run a clinical trial.

4)    What was your most fun or inspirational time in the lab/science?

I cannot really pinpoint a specific time. I really love my job and I enjoy being creative, getting to ask questions and trying to solve problems.  I chose a career in science as I really enjoyed it.  I think so long as you pursue a career because it makes you happy, you will find inspiration in many places. 

5)    What was your biggest career or scientific disappointment and how did you overcome it?

I feel there are disappointments in science that I have as a faculty member which were present, but not as apparent, when I was a postdoc.  These include both grant rejections, and manuscript rejections.  With grant rejections I’m a bit like Tigger, and I bounce back…or submit another grant.  I find paper rejections harder to deal with as you can’t bounce back in the same way as you have to submit your work to another journal.  I feel that editors will often give a more established researcher the ‘benefit of the doubt’ and send a paper for review while for early career scientists getting past the editor is often the biggest hurdle.  

6)    Have you participated of any outreach or public engagement activities recently?

I spoke at Pint of Science last month, but I actually don’t drink pints….of beer.  I love red wine, port, and champagne.  I’d order a pint of champagne if possible ;-).  It was the second time that I’ve spoken at a Pint of Science event, and I’ve also spoken at an event called NerdNite.  That one is just for nerdy people; not necessarily scientists but anyone with a passion for something.  They are great fun as you have to tailor your talk to your audience. 

Find out more about Harry Leitch's research.

1. What was your journey through science so far? 

I’ve had a bit of a complex route. I started off by studying medicine at Fitzwilliam College, Cambridge. I took a year out in 2006 to compete at the my first Commonwealth Games, and when I returned I decided to spend the summer in a lab – mainly so I could hang around Cambridge and be there for all my friends graduating. Until then I had no inclination that I was interested in basic science or research, and I’d always hated undergraduate practical classes. However, from almost the moment I started I felt completely at home in the lab, and the research environment. I loved the creativity, and coming to work each day to solve a problem or conundrum, however small – and in those days they were very small problems (why didn’t my restriction digest or PCR work…). I was lucky to work with Bill Colledge and he taught me everything – how to pipette, mini-preps, tissue culture. Although his lab was by that time focussed on reproductive endocrinology he has a long history in the ES cell and knockout mouse field, having been a postdoc with Martin Evans. It was reading around this topic which was really the catalyst for my ongoing interest in pluripotency and stem cell biology.

I ended up spending over a year in Bill’s lab, including my 3rd year project, and after this it was a no-brainer to apply to the MB/PhD programme at the clinical school – luckily, I was accepted. So, after a year of medical school, I started a PhD joint supervised by Azim Surani and Austin Smith, and I was also lucky to work closely with Jenny Nichols – three fantastic PIs. I combined the interests of the two labs by studying pluripotency in primordial germ cells (PGCs) – with a thesis entitled ‘Pluripotency and the germline’. My core interests haven’t changed too much over the years – when I started my lab I made a huge departure and called it ‘Germline and Pluripotency’(!). I managed to finish my PhD in two and half years, which bought me time to do a postdoc before returning for my final two years of medical school (although I eked out at least another year’s-worth of postdoc in evenings and weekends during this time).

After finally graduating from medicine in 2014 (having started in 2003), I worked as a junior doctor in Cambridge for a year before being attracted down to London by an innovative academic foundation year created by the MRC London Institute for Medical Sciences (LMS). This is part of their broader clinician-scientist programme – called the Chain-Florey Scheme -  which has been pioneered by the Director Mandy Fisher. This gave me some invaluable dedicated time back in the lab during which I hooked up with my long-time friend and collaborator Petra Hajkova. Working alongside Petra’s lab and benefiting from her excellent mentorship I was able to secure independent funding and have recently established my own group at the LMS. Clinically, I’ve specialised in paediatrics and continue to combine my research with specialist training – which keeps me busy and out of trouble! 

2. What research do you do and what do you think the impact is? 

Perhaps unusually for a clinician my research interests are in basic biology. Broadly speaking they span stem cell biology, pluripotency, germline development, epigenetics and reproduction. Most of my work focusses on the mammalian germline cycle. This provides a common thread to my research which allows me to think about a wide range of questions – such as studying how pluripotency is established and controlled in pluripotent stem cells and the embryo, characterising how germ cells are established and develop during embryogenesis, establishing culture conditions for germ cells, and researching the epigenetic changes in the germline. I enjoy working both in vitro – establishing simple systems to answer complex questions - and in vivo, where the real magic happens. The majority of the impact of my research is in answering fundamental biological questions, but I think these are fairly big questions about where we come from and what information we pass onto the next generation – things we just need to understand. However, this fundamental knowledge undoubtedly is important for a range of applications. For instance, in regenerative medicine approaches, we hope to inform work to safely and efficiently direct stem cells to make useful cell types. Also, the culture systems we are developing for germ cells and the information we are learning about their fundamental biology (including their epigenome) may well be of direct relevance for attempts at in vitro gametogenesis – making sperm and eggs in the dish. This could have a significant impact on reproductive medicine and fertility treatments. However, my strong belief is that if you do interesting, creative research on important questions then there will be impacts and spin-offs that you never even thought of – in fact, I think evidence suggests this is the way things tend to happen.

3. What are your next steps? 

I guess the next few years are all about making progress with the projects we’ve started and, hopefully, building up a successful independent research program. I’m really excited about the projects we have in the lab, but understandably anxious that they come to fruition. Luckily, I’ve just recruited some fantastic people and building a strong team is also something that I’m passionate about. Clinically, I have a fair amount of training to do and I need to think about carving out a niche in which I can make a valuable clinical contribution, in addition to managing the lab. Imperial College, Imperial NHS Trust and the MRC LMS have been very supportive so far - and there may be some exciting possibilities in the future. The flip side is, it could all be a massive disaster… but I guess that’s what gets me out of bed in the morning.

4. What was your most fun or inspirational time in the lab/science? 

I’m a strong believer that each new step forwards should be more exciting than the previous one, and I’m really enjoying where I am right now. Being a group head is a fantastic opportunity. Of course, it’s also absolutely terrifying... and everything they say about the admin overload is 100% correct. However, it’s what I signed up for, and so I can’t complain too much. I hope in 5 years’ time things will be even more fun and inspirational. If not, there’s always bar work… 

5. What was your biggest career or scientific disappointment and how did you overcome it? 

Oh god. There are far too many to mention. I sometimes think research is about staying positive while stumbling from one colossal disaster to another – something I learned a lot about from my sporting background. I competed in three Commonwealth Games, and came 4th twice – so never got the medal I was after. That’s proper disappointment! Like almost everyone in science there’s been positions I didn’t get that I wanted, experiments and projects that failed, and bad reviews or feedback I’ve taken pretty personally. However, there’s almost always a smattering of good news to keep you going and of course the good times balance out the disappointments. For this reason, I think it’s important to celebrate victories – however small. If you can’t enjoy the good times, then why put up with all the crap! I’m probably a bit junior to be dishing out sage advice but I’ve always thought if you’re passionate about what you do and have self-assuredness that you’re doing the right thing, then things work themselves out eventually. It’s also really important that you surround yourself with people who give you high quality and honest advice, so you can question what you’re doing and update your plans if necessary. There’s plenty of bad advice out there which should be ignored at all costs. Having humility and open-mindedness is really important, but at some points you have be stubborn too. 

6. What is your cocktail of choice?   

Good question! I think the most important thing is the bartender. If someone can mix a good drink then I tend to stick with the classics – boozy as hell and something that will hit you for six. Hard to argue with a proper Martini, Old Fashioned or Manhattan. 

Find out more about Dr Sattler's research

What was your journey through science so far?

I obtained my PhD from the Medical University in Vienna, Austria, and then took up my first postdoctoral position at Imperial College. My PhD project was to characterize a family of newly identified pattern recognition receptors, traditionally considered part of the immune system, but we found them on endothelial cells. This was my first step towards the realisation that there is more to the immune system than defense from infectious diseases. During my first postdoctoral project, I worked on regulatory immune cells and their potential therapeutic benefit in autoimmune disease and in 2012, I joined Nadia Rosenthal and Sian Harding at the NHLI to explore the role of the immune system in heart regeneration.

What research do you do and what do you think the impact is?

Our research focuses on what happens to the immune system after a myocardial infarct. One in five heart attack patients go on to develop heart failure. There is no cure and prognosis is very poor. There is increasing evidence that the immune response to the initial damage has an important role to play in the development of heart failure and understanding what exactly happens will be the first step to a potential new therapeutic target.

I currently lead a BHF-funded project investigating how the adaptive immune system influences regenerative responses after myocardial infarct and what impact it has on the progression to heart failure. This overarching project bridges immunology, regenerative medicine and cardiovascular biology and includes imaging, biomaterial and genetic approaches.

I’m lucky to work with a fabulous team of enthusiastic researchers, students and multi-disciplinary collaborators to tackle a few crucial questions in cardiac regenerative medicine; Does a myocardial infarct induce anti-heart autoimmunity and does this indeed have a clinically relevant impact on recovery? Can we modulate the immune response to prevent this reaction and boost regeneration? Can we predict development of heart disease in autoimmune patients based on genetic factors or biomarkers?

Understanding the still vastly underappreciated impact of the immune response to tissue damage will allow us to eventually modulate it in a way to boost its profound regenerative capacity while avoiding excessive inflammation and fibrosis and subsequent development to heart failure. Importantly, I strongly believe that an immune-modulatory component will be an essential part of regenerative therapies to ensure cell- or biomaterial-based strategies can fulfill their full potential without being hampered by ongoing and persistent inflammation and tissue damage. There have in fact been a range of clinical trials so far on immuno-modulatory interventions in heart attack patients, but severe limitations in design and measured readouts mean that is still impossible to give a sensible answer to effectiveness of these treatments.

What are your next steps?

We still have a lot to understand and a long way to go until we will be able to design efficient interventions targeting the immune system for regenerative medicine, because the immune response is stupendously complex and context dependent. We hope to be able to contribute a few pieces to the puzzle.

What was your most fun or inspirational time in the lab/science?

I have thoroughly enjoyed the last few years working in Sian Harding’s Cardiovascular Section of the NHLI, and a very close collaboration with Nadia Rosenthal and Muneer Hasham at The Jackson Laboratories in the US. Sian Harding’s Section is a beautiful example of how – despite increasing pressure and competitiveness of the overall scientific environment - a group of scientists of a variety of specialties can work together in an open, friendly and truly supportive environment. I have several collaborative projects bridging specialties and groups and I never have problems finding enthusiastic collaborators for my most risky ideas. I’m convinced that academic research should be about pooling brain capacity and being able to openly share and discuss ideas, and in my current position I always feel confident to do that.

What was your biggest career or scientific disappointment and how did you overcome it?

I am to the day still haunted by my PhD project. One of the aims was to find a ligand for a newly identified receptor. Being incredibly short of funding, we were very resourceful in getting our hands on a variety of potential ligands, but couldn’t afford a more systematic approach. Needless to say, we did not identify the ligand, nor has anybody since, but I keep checking the literature hoping that eventually somebody will solve the mystery.

Career disappointments on the other hand, are something rather universal for most early stage researchers at this point in time. Faculty positions in research institutions have the status of rainbow unicorns, and at the same time finding external funding for personal support gets very hard at a certain level of experience. The key is not to allow this constant threat to invade daily thinking. ‘Enjoy it while it lasts’ has been my personal mantra for many years.

Have you participated in any outreach or public engagement activities recently?

Yes, it’s fun! It’s hard to find the time, but I always thought it was worth it, no matter if I was knitting microglia or teaching a class of primary school kids what science really is about. I went to be a judge at a school science fair and to a profession-speed dating session. I regularly have work experience students in the lab. It’s little effort and may have a huge impact on the student’s future. When I was a child, somebody at some point must have inspired me to go to university and study Biology. Now I get up happy and motivated every day, because I have an interesting job I love. Everybody deserves this chance!

Find out more about Dr Michail Klontsaz' research

What was your journey through science so far?

What research do you do and what do you think the impact is?

What are your next steps?

What was your most fun or inspirational time in the lab/science?

What was your biggest career or scientific disappointment and how did you overcome it?

Have you participated in any outreach or public engagement activities recently?

Find out more about Delfim Duarte

WHAT WAS YOUR JOURNEY THROUGH SCIENCE SO FAR?

I graduated in Medicine at the University of Porto in Portugal. As an undergrad, I studied angiogenesis and inflammation in Raquel Soares’ lab. During medical school, I was selected for a summer placement in Tom Kirchhausen’s lab (Harvard Medical School) and there I used a single-molecule approach to study the GTPase dynamin during clathrin-mediated endocytosis. I then carried out a Master’s project on platelet and endothelial cell microparticles in asthma patients. As a consequence of these experiences, I became very interested in cancer, vascular biology, cell-to-cell communication, and microscopy. I saw Haematology as a discipline where I could study these topics and have an impact as both a doctor and as a research scientist. After starting the specialty of Haematology in the Portuguese Institute of Oncology, in Porto, I was given the opportunity to pursue a PhD in basic/translational haematology. I was selected for the GABBA PhD program (gabba.up.pt) and joined Cristina Lo Celso’s lab at Imperial College in 2014. 

Find out more about Dr Gabor Foldes' research

WHAT WAS YOUR JOURNEY THROUGH SCIENCE SO FAR?

I graduated from Semmelweis University, Budapest in 1998, where four years later I also got my PhD. I trained in Medicine and then specialised in Internal Medicine and Cardiology ten years ago. So I am a medic by training but since my university years, I have also been involved in research in various cardiovascular areas that interest me. In the middle of my Cardiology rotation back in 2006 I was awarded a fellowship by the Novartis Foundation and spent five months in Professor Ken Chien’s laboratory at Harvard. This was my first opportunity to get involved with stem cells. Our aim there was to grow multipotent islet-positive heart progenitors from mouse embryonic stem cells. When sometimes we went in the ‘wrong’ direction with the differentiation and found beating heart muscle cells under the microscope, everybody in the lab was so disappointed! Such a bad protocol, complained everybody. It has now been more than nine years since I started working with Professor Sian Harding at the National Heart and Lung Institute. Our group has also been focusing on the differentiation and characterisation of cardiovascular derivatives of human pluripotent stem cells. Our aim now is, in fact, the complete opposite: generating those beating cells, no matter what. The more beating, the better!

WHAT RESEARCH DO YOU DO AND WHAT DO YOU THINK THE IMPACT IS?

What I’m most interested in, probably because of my clinical background, is the translation of human pluripotent stem cells from heart disease models in a dish, to real cardiac repair. As well as driving various heart muscle cell projects, for some time I have also been leading new projects on stem cell-derived vascular cells. In 2010 I was also appointed as Associate Professor at my other institution, the Heart and Vascular Centre, Semmelweis University in Hungary.  That position allows me to leverage the specialist in vivo imaging expertise of my colleagues there. Being involved in this type of joint effort, and having that extra support, has been very helpful when trying to exploit such a complex technology.

WHAT ARE YOUR NEXT STEPS?

My hope is that, by using these endothelial cell constructs, we’ll be able to generate something that resembles the native vessels. I think vascular scaffolds as a supporting microenvironment can be well used to support tissue repair or even replacement. When talking to my clinical colleagues, it often comes up that a new engineering design of a responsive, living conduit similar to a native vessel would be very much welcomed. Given the substantial clinical challenges of vascular disease, I think it is crucial to develop something which is suitable for application in tissue-engineered vessels and with favourable properties of strength, surface, anti-inflammation and long-term durability. I also see these ideas receiving a lot of support in-house and from many of our collaborators around Europe. All these collaborations would substantiate the potential of these cells in therapy and may even promote their further development as a first-in-man implantation.

WHAT WAS YOUR MOST FUN OR INSPIRATIONAL TIME IN THE LAB/SCIENCE?

Stem cell research generates a great deal of interest, and many people want to hear or talk about it. Everybody has questions for us, or just sharing some secret hopes that various diseases in their family could be cured with a bit of stem cell cocktail. Not surprisingly, I have received numerous invites and had the opportunity to present this work around the world. I am most proud of my stem cell image which was showcased in front of the London Eye, where a never-ending line of tourists tried to take selfies with it for days. I also have fond memories of the award for my high content imaging work being presented at the top of Fairmont Hotel in San Francisco. These moments keep you going.

 WHAT WAS YOUR BIGGEST CAREER OR SCIENTIFIC DISAPPOINTMENT AND HOW DID YOU OVERCOME IT?

I fully agree with some recently published editorials in Nature and other journals that young scientists are facing a tougher and much more competitive workplace than many of our senior colleagues did at the same stages of their own careers. Unfortunately, we cannot underestimate the burden of grant preparations: a colossal amount of our time - measured at least in months - spent on each application. With suc­cess rates for most grants being very low recently, many times these ideas, even the ones we found particularly strong, are going down the sink. The bottom line is that even if we carry out exceptional science, we might still experience a bad combination of limited resources and increased pressure. While we’re aware that a stem cell project is rarely without any risk, it would be great to see bolder decisions and less risk aversion around grant decisions.

HAVE YOU PARTICIPATED IN ANY OUTREACH OR PUBLIC ENGAGEMENT ACTIVITIES RECENTLY?

Over the years many high school students and young undergraduates visited our lab to look around; some even to spend a summer (one advantage of bad London weather) with us. Most of the time they are very switched on, and their short visits are often followed by further work in the lab. One of them even participated with success at various innovation contests for young scientists such as Intel’s International Science and Engineering Fair last autumn.

Find out more about Dr Paolo Campagnolo's research

WHAT WAS YOUR JOURNEY THROUGH SCIENCE SO FAR?

I graduated in Biotechnology at the University of Padua (Italy) with an experimental thesis on gene and cell therapy in 2005, when this was a relatively new topic. I then moved to Bristol (UK) for my PhD, working on the isolation of a novel progenitor population from human saphenous vein leftovers from cardiac patients. This turned out to be a pretty interesting population of cells, able to promote vascularization of ischemic tissues both in peripheral limbs and infarcted hearts. Following this, I worked at King’s College London on the use of tissue engineering to prepare vascular grafts for coronary bypasses. In these projects, I worked on the differentiation of stem cells to be seeded on decellularized blood vessels in a bioreactor to produce synthetic vessels resembling the natural structures. This experience encouraged me to decide to focus my research on the interaction between cells and biomaterials. I therefore joined Imperial College London, working in the Materials Department in the lab of Prof Stevens, one of the best labs in this field. At Imperial I collaborated with a number of very talented material scientists, as a result we devised a new synthetic material for vascular grafts and developed a nanomaterial-based system for in vivo gene therapy. More recently, I have been appointed as a lecturer at the University of Surrey, where I am working to establish my own research group.

WHAT RESEARCH YOU DO AND WHAT DO YOU THINK ITS IMPACT?

My main research topic is the use of endogenous/adult stem cells for tissue engineering applications and in particular for the development of bypass/graft substitutes (large vessels). So far the cell population I have isolated during my PhD is approaching human clinical trial phase, thanks to my initial work and to the valuable contribution of so many other talented and determined people. My more recent work on tissue engineering and nanomaterial-based gene therapy is still under development, but I hope one day it will become clinically relevant.

WHAT IS THE NEXT STEP?

In September I started at the University of Surrey as a lecturer in Molecular Cardiovascular Biology. In my new appointment, alongside some teaching duties, I will be setting up my research group (and lab). My research interests focus on the use of biomaterials and stem cells to produce a model of the vascular wall and the use of a bioreactor to mimic the pathophysiological conditions experienced by the vascular cells in vivo. The model will allow the study of cell-cell interactions and leukocyte extravasation in normal and pathological conditions. Establishing an in-vitro model of the vasculature enables the study of several diseases and their vascular complications, such as diabetes and viral infections.

WHAT WAS YOUR EXPERIENCE WITH CO-ORGANISING THE ISRMN NETWORK?

I really enjoyed co-organising the meetings of the ISRMN, it has given me the amazing opportunity to interact and network with many interesting and valuable colleagues by challenging my natural awkwardness. It has made me also more aware of the organisational hurdles and the amazing feeling of accomplishment that comes with putting together a successful meeting. Of course, the interaction with Dina and Marta has been very constructive and taught me to value different approaches and inspired flexibility and passion for science.

WHAT WAS YOUR MOST FUN AND MOST INSPIRATIONAL TIME IN THE LAB/ IN SCIENCE?

During my PhD, I used to spend a lot of time in the lab, almost never sitting at my desk (a luxury that I don’t have anymore) and my mood used to depend a lot on my results, although lately, I have learned that your mental health depends on being more detached. I still remember the day I burst into my PhD supervisor’s office (yes, literally…he is a very understanding man) shouting: I have got some cells!!! They grow like embryoid bodies. And he said: No way! If it’s true we will call them ‘Paoloids’ (we are both called Paola/o). I think his support during my rather difficult PhD and his enthusiasm not only made me work super hard but also showed me what real passion for science is.

WHAT WILL YOU MISS FROM IMPERIAL COLLEGE?

Imperial is a great institution with amazing resources and facilities that are surely unparalleled. But most of all I will miss the people I met here. I had the chance to work with great minds and this was at the same time humbling and encouraging.

ANYTHING ELSE?

Overall, I would say that is important for young scientists to learn that failure and patience are two inevitable facts of the scientific life. This is not to say it’s sad or not worth the effort; it is to say that everyone experiences the same setbacks as you and these difficulties are only stepping stones which will form your character and create the correct attitude to develop your career. I want to say this because many valuable scientists (and especially many women, including me) tend to feel alone in their path to success and give up thinking other people have it easy.