PhD Studentships currently available:

3 year EPSRC PhD studentship "Synthetic Biology"

Synthetic Proteins for Nanotechnology

Area: Engineering Theme - Synthetic Biology

Supervisor: James W. Murray -  j.w.murray@imperial.ac.uk

 Natural enzymes catalyse reactions with rates and specificities that are unmatched by artificial catalysts. The proteins that achieve these reactions often fold spontaneously but have a structure assembled with atomic precision. The general protein folding and design problem is unsolved. I propose to simplify the protein design problem by removing the need for monolithic protein folds. Instead, a synthetic extensible scaffold is used with a repeated sequence motif. The scaffold is incrementally extended with designed loops that may be functional. This allows the iterative modular construction of individual functional subunit insertions which can then be composed into a larger scaffold with defined relative spatial positions. We have developed a synthetic extensible scaffold protein, SynRFR, that supports inserted loops, and several of crystal forms, see Fig. 1 and MacDonald et al (2016). The loops were designed using "fragment-free" protein backbone, not based on any known structure, which is different to most published protein design methods. The student will develop the published proof of concept in this proposed project.

Firstly, generating a metal site on an extended loop, which would be expected to have superoxide dismutase activity, as a model synthetic enzyme. Secondly, binding more complex cofactors, such as a heme between two extended loops, and to combine these cofactor sites and loop extensions, as in Fig. 2. This project is a new way to create protein-based nanostructures and devices, with applications in synthetic enzyme design. We would expect the work to be mainly computational, particularly in the early stages of the project. Would suit a numerate biochemist or physics, maths or computer science graduate.

Fig 1. (a) SynRFR crystal structure showing the beta-solenoid, central repeat region (green) and N- and C- terminal caps (blue and red). (b)-(d) Three different experimental SynRFR crystal lattices in space groups P4122, R32 and P3221.

 

Fig1

 

 

Fig 2. A model of an extensible scaffold with two modules inserted.

Fig 2

 

 

 

 

 

 

 

 

Reference:

 MacDonald, J. T., B. V. Kabasakal, D. Godding, S. Kraatz, L. Henderson, J. Barber, P. S.Freemont, and J. W. Murray (2016). Synthetic beta-solenoid proteins with the fragment-free computational design of a beta-hairpin extension. PNAS 113(37), 10346–103.

Eligibility and how to apply:

Candidates must have, by October 2018, a BSc at 2:1 level or better and, in addition, a Masters degree at Merit level or better. Exceptional candidates without a Masters degree might be considered. Only UK or EU nationals who have been resident in the UK for the last 3 years are eligible. The studentship must commence in October 2018.

The studentship covers tuition fees and provides a tax-free stipend of about £16,777 per year.

Informal enquiries to j.w.murray@imperial.ac.uk.

Applications must be submitted to James Murray [j.w.murray@imperial.ac.uk] and must contain a full CV, a personal statement and the contact details of 2 academic referees.

The deadline for receipt of applications is 10th August 2018.

BBSRC DTP-funded PhD Studentship on "Engineering the Pulmonary Epithelium 'on a chip' to Investigate Immune Responses"

Imperial College London's BBSRC Doctoral Training Partnership programme is pleased to announce a 3-year, fully-funded PhD studentship starting in October 2018. The project is titled "Engineering the pulmonary epithelium 'on a chip' to investigate immune responses to the inhaled external environmental stimuli" and is co-supervised by academic researchers at Imperial College London's National Health and Lung Institute and the Department of Bioengineering.

Project Summary: Recent ‘lung on chip’ technologies capture organ-level physiology within an in vitro framework that is amenable to manipulation and visualization [1]. Such approaches herald unprecedented experimental paradigms, for example the ability to study patient’s own cells within a bioengineered microenvironment that faithfully mimics the biomechanical and biochemical cues that dictate in vivo function, all while reducing animal use. We will develop a pulmonary epithelium ‘on a chip’ that mirrors the key structures, interfaces and physical forces that dictate the immune response to inhaled allergens and pathogens. This has 3 components: (i) the epithelial cells themselves, including ciliated columnar, goblet and Club cells that together create the epithelial barrier; (ii) the air-liquid interface needed to differentiate the epithelium; and (iii) airway macrophages that define the immune response that were absent from prior “on chip” models [1]. We are particularly interested in the interactions between immune cells, airway epithelial cells and local stimuli such as physical forces, oxidative stress, microbial stimulation and inhaled pollutants [2]. We will use cells isolated from the respiratory tract of healthy and diseased patients to investigate the epithelial barrier during stress and disease, to identify molecular mechanisms underlying disease, including biomarkers and new drug candidates. 

References:

[1] KH Benam et al., 2016. Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Nature Methods. 13:151-7.

[2] CM Lloyd & S Saglani. 2010. Asthma and Allergy: the emerging epithelium. Nature Medicine, 16:273-274

How to apply: Initial applications should include a full CV, a personal statement (500 words max) as well as the names, addresses, and contact details of two academic referees. Completed applications should be submitted to Professor Clare Lloyd at c.lloyd@imperial.ac.uk by Friday, 31 August 2018. Please note only shortlisted applicants will be contacted by the project supervisors for in-person interviews. 

Informal enquiries are welcomed and should be sent Professor Clare Lloyd, c.lloyd@imperial.ac.uk or Dr Darryl Overby, d.overby@imperial.ac.uk.

Eligibility: Applicants are expected to hold, or to be awarded a first class or a good upper second class BSc Degree, or an equivalent qualification, in addition to a Masters degree in a relevant subject (preferably bioengineering) before October 2018. Only UK and EU students who meet the UK residency requirements are eligible to apply (minimum of three years of continuous residency in the UK immediately prior to the start of the PhD). Non-EU nationals are not eligible.

Funding: The studentship covers tuition fees and provides an annual tax-free stipend of about £16,700 per year. A yearly training and research costs allowance is provided. 

PhD in Plant Epigenetics and Regeneration

Four-year fully funded PhD position in the group of Dr Jie Song, at the Department of Life Sciences, Imperial College London

This project is focused on the investigation of regeneration at the chromatin level, in the model plant Arabidopsis. In a multicellular organism, cells are differentiated throughout development. The information of cell identity is heritable and is coded beyond the DNA sequence, e.g. by Polycomb-based chromatin modifications. In plants, however, this epigenetic memory can be wiped off and adults can regain stem cell properties to enable regeneration. The student will study the antagonistic mechanisms, silencing by Polycomb and gene reactivation by epigenetic reprogramming. The student will also develop novel tools to manipulate this process, which will be useful in both fundamental research and the biotechnology industry.

Informal inquiries are welcome and should be sent to Dr Song (j.song@imperial.ac.uk).

Eligibility:
The candidate is normally expected to have a BSc degree at 2:1 level or better and a Masters degree at Merit level or better, by October 2018. Exceptional candidates without a Masters degree may be considered.

How to apply:
Please email Dr Song (j.song@imperial.ac.uk) and include in your application:
• A cover letter
• Your CV
• All available transcripts
• Arrange for three references to be send directly from the referees
Applications are accepted until the position is filled.

Funding notes:
The studentship is funded by the Royal Society. It will cover the cost of university fees at UK/EU rate (£4,195 p.a) and the student’s stipend (approx. £16,5K p.a.).

4 year iCASE PhD studentship On-Column Monitoring of Protein Purification by Spectroscopic Techniques

4 year iCASE PhD studentship

 On-Column Monitoring of Protein Purification by Spectroscopic Techniques: Professor Bernadette Byrne and Professor Sergei Kazarian

 Applications are invited for a 4 year iCASE PhD studentship position fully funded by the BBSRC and GSK and based in the Departments of Life Sciences and Chemical Engineering at Imperial College London.

 Monoclonal antibodies (mAbs) represent effective therapies for the treatment of a range of chronic and life threating diseases including rheumatoid arthritis and cancer. However, the cost of production of therapeutic antibodies is significantly higher than small molecule drugs, mainly due to the complex isolation process which involves a very expensive Protein A affinity capture step.

 This project builds on our previous research showing the power of Attenuated Total Reflection Fourier Transform Infrared spectroscopy (ATR-FTIR) for probing the build-up of contaminants and the effects of cleaning protocols on resin life span using ex situ resin beads and a microfluidic set up (Boulet-Audet et al. 2015, Analytical Bioanalytical Chemistry 407, 7111–7122; Boulet-Audet et al, 2016, Scientific Reports 6, 30526). This project focuses on the further development of novel spectroscopic approaches to directly monitor the Protein A affinity capture step, on-column. For this we can use Raman spectroscopy, where a laser beam will probe through a small window in the column and the backscattering produced will be used in confocal mode giving information on what changes are taking place at a range of depths (up to ca. 200 µm with steps of 1-3 µm). In this project, we also aim to explore linking a single column with focal plane array detector for FTIR imaging, allowing multiplexing of many signals from different locations in a column simultaneously. The findings from these studies will provide novel insights into the causes and cures of resin decay and validate new systems with the potential to be of widespread use to industry. This project will provide excellent training for the student in areas as diverse as biopharmaceuticals, protein purification, chromatography, Raman spectroscopy and FTIR spectroscopic imaging and will include a secondment to GSK.

 Applicants should have a BSc in Chemistry/Chemical Engineering or related discipline, at 2:1 level or better, and an associated Masters degree or an equivalent level of professional qualifications or experience. Knowledge and experience of relevant spectroscopic techniques is highly desirable but not essential.

UK or EU candidates, who have lived in the UK for 3 years, are eligible for this studentship.

 

Closing date for applications: 31st May 2018

 

Further details on this project are available from Professor Bernadette Byrne b.byrne@imperial.ac.uk and Professor Sergei G. Kazarian s.kazarian@imperial.ac.uk. Information about the research groups is available at www.imperial.ac.uk/people/b.byrne and www.imperial.ac.uk/people/s.kazarian.

EPSRC funded 3 year PhD studentship.

EPSRC funded 3 year PhD studentship.

 A 3-year EPSRC funded PhD studentship is available, starting from October 2018, to work in the laboratory of Giorgio Gilestro, in the Department of Life Sciences at Imperial College London. The candidate will be an enthusiastic student, passionate about science and interested in solving some of the most puzzling problems of neuroscience. 

The main research focus of the laboratory is to uncover the yet mysterious function of sleep, but we also have projects on behavioural neurobiology and bioinformatics. Most projects belong to wider collaborative enterprises between our laboratory and partner laboratories in the Computer Science and Bioengineering Departments of Imperial College London, one of the best Universities in the world, located right in the heart of London.

Previous work of the lab in the field of bioinformatics and computational biology include:

 The Department of Life Sciences is a leading department of Biological Sciences among UK Universities and has consistently been awarded the highest research rating. In the 2014 REF assessment, the Department was ranked first in the Research Intensity table compiled by The Times Higher Education.

 The candidates should have a strong background in quantitative sciences and an interest in neuroscience. The goal of the project is to apply machine learning to better understand sleep – and vice-versa. Some preliminary experience with programming and/or machine learning is required.

Candidates must have, by October 2018, a BSc at 2:1 level or better and, in addition, a Masters degree at Merit level or better. Exceptional candidates without a Masters degree might be considered. Only UK or EU nationals who have been resident in the UK for the last 3 years are eligible.

The studentship covers tuition fees and provides a tax-free stipend of about £16,700 per year.

To apply, please send a copy of your CV, a short paragraph describing your interests and your achievements to giorgio@gilest.ro

The deadline for applications is 30th June 2018. Informal enquiries are very welcome.

 

3 year fully funded PhD studentship starting October 2018 as part of a new Cystic Fibrosis Trust

A 3 year fully funded PhD studentship starting October 2018 as part of a new Cystic Fibrosis Trust- funded Strategic Research Centre at Imperial.

PhD with Dr Huw Williams (Life Sciences) and Prof Jane Davies (Medicine) Imperial College London.  (h.d.williams@imperial.ac.uk ).

The individualised innate immune response in CF infection:  increasing fundamental understanding and identification of bacterial biomarkers of inflammation.

Hypochlorous acid (HOCL) produced by neutrophil myeloperoxidase (MPO) and hypothiocyanous acid (HOSCN) by the DUOX/LPO system of the airway epithelium are potent antibacterial products of the innate immune system  (Odobasic et al., 2016). However, in Cystic Fibrosis prolonged neutrophil recruitment fails to resolve infection leading to a damaging inflammatory cycle and progressive lung damage, in part due to the action of these thiol reactive oxidants (Williams & Davies, 2012, Winterbourn et al., 2016).

Inflammatory biomarkers could play a critical role in the development of anti-inflammatory therapies and reflect downstream improvements in CF-lung disease for individualised disease-modifying treatments (Muhlebach et al., 2016), but recent interventional trials fail to show significant changes in sputum inflammatory markers (Muhlebach et al., 2016, Horsley et al., 2013).  We hypothesise that infecting bacteria, such as P. aeruginosa, will produce bacterial biomarkers that will be indicators of the innate immune activity encountered in the CF lung.  

Building on preliminary work, this PhD will: (i) identify and validate redox-specific bacterial biomarkers based on gene expression and/or redox-proteomics-based analyses of the response of P. aeruginosa to HOCL and HOSCN, (ii) use redox biomarkers to address key questions in Cystic Fibrosis infection biology, and (iii) elucidate HOCl and HOSCN- specific protection and repair mechanisms in this opportunistic pathogen.

Experimental approaches: The project will involve some/all of the following experimental approaches: gene expression studies using qRT-PCR and RNA-seq, quantitative mass spectrometry-based proteomics, cell biology work with neutrophils, air- liquid interface cultures and patient samples, bacterial molecular genetics and biochemistry.

Who should apply: This PhD will suit a student with a BSc degree at 2:1 level or better and a Masters degree, at Merit level or better, in Biochemistry, Biological Sciences or related discipline with interests in studying oxidative stress damage and protection mechanisms in a clinically important context. Exceptional applicants without a Masters degree might be considered.

Funding:  The student will receive a tax-free stipend of £22,278 in year 1 rising to £26,057 in year 3, and fees will be paid at the UK/EU fee rate. Non UK/EU applicants are not eligible.

 The deadline for applications is 4th June 2018 and candidates should submit a full CV and the names and contact details of 2 academic referees to Dr Huw Williams (h.d.williams@imperial.ac.uk) by the deadline.

 Horsley, A.R., J.C. Davies, et al (2013) Changes in physiological, functional and structural markers of cystic fibrosis lung disease with treatment of a pulmonary exacerbation. Thorax 68: 532-539.

Muhlebach, M.S., J.P. Clancy, S.L. Heltshe, A. Ziady, T. Kelley, F. Accurso, J. Pilewski, N. Mayer-Hamblett, E. Joseloff & S.D. Sagel, (2016) Biomarkers for cystic fibrosis drug development. J Cyst Fibros 15: 714-723.

Odobasic, D., A.R. Kitching & S.R. Holdsworth, (2016) Neutrophil-Mediated Regulation of Innate and Adaptive Immunity: The Role of Myeloperoxidase. J Immunol Res 2016: 2349817.

Williams, H.D. & J.C. Davies, (2012) Basic science for the chest physician: Pseudomonas aeruginosa and the cystic fibrosis airway. Thorax 67: 465-467.

Winterbourn, C.C., A.J. Kettle & M.B. Hampton, (2016) Reactive Oxygen Species and Neutrophil Function. Annu Rev Biochem 85: 765-792.

BBSRC iCASE project on The Role of Fibins in Gill Development, Inflammation and Remodelling

Supervisors: Professor Maggie Dallman and Dr Laurence Bugeon
 

Throughout the life course our respiratory system is exposed to a number of assaults such as pollutants (diesel particulates, nitric oxide, silica, cigarette smoke etc) and a variety of pathogens and allergens. Prolonged or repetitive insults can lead to irreversible damage of the lung. In order to address this, whilst one approach is to reduce exposure to such harmful irritants, another is to identify molecular pathways that could be targeted to improve the outcome of such damaging exposure and enhance tissue repair. 

Using the zebrafish as a model organism we have found that the fish gill can be used to model the inflammatory response of mammalian lung. We have gone on to find that the zebrafish has an extremely efficient gill repair mechanism and is very resilient to injury compared to mammals which are prone to develop irreversible fibrosis consequent to similar assaults. 

We have identified candidate genes that are upregulated in fish and downregulated in mammals during biological processes leading to scaring and fibrosis in mammals. The fibins fall into this category. Taking advantage of such differences between fish and mammalian systems, this project aims to discover the function of these poorly described genes (the fibins) that otherwise play a critical role in fish development. 

The Dallman lab is looking for a talented and motivated PhD student to study the fibins. Experimental approaches will include gene cloning, imaging, gene expression analysis, transgenic fish maintenance. Funded by an iCASE award through BBSRC and Boehringer Ingelheim, the student will work closely with our industrial partners, including periods of working at one or more of their sites. iCASE research students must spend part of their time with the non-academic organisation. This placement is a compulsory and integral part of the training and must be a minimum of 3 months during the four-year period of the studentship.

Eligibility
Candidates should hold, an Upper Second Class Honours BSc degree or better or an equivalent qualification. Candidates with a Masters degree (at Merit level or better) in addition to the BSc may be given preference. They should have a strong academic background in the biological sciences and a desire to pursue research in line with that of the research group. Posts are open to UK nationals. EU nationals, who have spent at least 3 years prior to the application resident in the UK, are also eligible to apply. Non-UK/EU candidates are not eligible.

Funding
Funding from BBSRC and Boehringer Ingelheim will cover tuition fees for the four-year duration of the studentship, contribution towards project costs, and an annual tax-free stipend at the standard Research Council rate, for 2018/2019 - £16,777. This stipend will increase in line with the annual GDP deflator.
 
How to Apply
To apply for this position, please email a single PDF file including: a brief cover letter describing your relevant interests and research experience, your CV, and names and contact information of three referees with the subject line “fibins PhD” to Prof Maggie Dallman and Dr Laurence Bugeon; m.dallman@imperial.ac.ukl.bugeon@imperial.ac.uk
 
Key Dates
Deadline is 5pm on Wednesday, 5th September 2018
Interviews are scheduled to commence on Monday, 17th September 2018

QMEE NERC-funded PhD Studentship on Plant-atmosphere Interaction in Near-real Time

The Centre for Docotral Training in Quantitative and Modelling Skills in Ecology and Evolution (QMEE) is pleased to announce a 3-year, NERC-funded PhD studentship project to work on "Plant-atmosphere interaction in near-real time: eco-evolutionary optimality theory applied to carbon, water and energy cycle forecasting." This is a CASE project joint with the European Centre for Medium-Range Weather Forecasts (ECMWF). For additional information on the project, please click here

How to apply: Please email a covering letter and CV to Professor Colin Price at c.prentice@imperial.ac.uk. Applications received before 25th July 2018 will be given priority.

Eligibility: Candidates must have, by October 2018, a BSc at 2:1 level or better and, in addition, a Masters degree at Merit level or better. Exceptional candidates without a Masters degree might be considered. Only UK or EU nationals who have been resident in the UK for the last 3 years are eligible.

Funding: The studentship covers tuition fees and provides a tax-free stipend of about £16,700 per year.

MRC Funded 3.5 year Studentship

Key information

Supervisor: Dr Tiago Costa 

Project Title: Structural analysis of the Legionella pneumophila type IV secretion system by single particle cryo-electron microscopy.

A 3.5-year MRC funded PhD studentship is available, starting from October 2018, to work in the laboratory of Dr Tiago Costa, in the Centre for Molecular Bacteriology and Infection (CMBI) at Imperial College London. The successful applicant will be joining an internationally-renowned Research Centre, within one of the world’s top research universities. 

Legionella pneumophila, (the causative agent of Legionnaires’ disease) developed a specialized type IV secretion system (T4SS), to transport >300 toxins, into host cells (Costa et al, Nat Rev Micro, 2015). Some of the characterized translocated toxins play a critical role in hijacking host cellular pathways to establish the intracellular niche where the bacteria survive, replicate and ultimately cause disease. 
The goal of the project is to investigate the atomic structure of the L. pneumophila T4SS using cutting-edge single particle cryo-electron microscopy (cryo-EM) (Costa et al, Methods in Molecular Biology, 2017). The near-atomic details obtained from the 3D structure will provide unique insights into how toxins are recruited by the secretion system, how is the secretion system gated, and which is the toxins route within the secretion system. The project will pave the way for rational design of drugs that will abolish toxin secretion preventing bacterial survival and disease. 

The project will provide training in the biochemical isolation and characterization of large membrane protein complexes, cutting-edge single particle cryo-EM data collection and processing (Costa et al, Cell, 2016). This work will take advantage of the state-of-the-art electron microscopy infrastructures located at the Francis Crick Institute and Diamond Light Source.

The studentship covers tuition fees and provides a tax-free stipend of £18,000 per year. 
Candidates should have a strong background in protein biochemistry and an interest in bacterial secretion systems. Some preliminary experience with cryo-electron microscopy is desirable but not essential. 
Candidates must have, by October 2018, a first class or upper second class Honours degree in biological sciences (or other appropriate science subject), and a Master’s degree or equivalent research experience in a relevant subject area. Only UK or EU nationals who have been resident in the UK for the last 3 years are eligible. 

Apply

To apply, please send a copy of your CV, and covering letter describing why you are suitable for this PhD studentship to Nicola Tingley (n.tingley@imperial.ac.uk). 

Closing Date: 27 July 2018

Contact us

Informal enquires can be sent to Dr. Tiago Costa (t.costa@imperial.ac.uk). 

Further information

Visit the MRC Centre for Molecular Bacteriology and Infection website