Project Description

This project aims to incorporate machine learning algorithms in data assimilation processes to improve efficiency and accuracy of wildfire estimations and predictions. The resulting models will assimilate data of wildfire variables (fire incidence, burnt area, fire duration, emissions etc) and wildfire drivers (a wide range, e.g. vegetation-related variables, climate related variables, human/society related variables etc). These data will be both qualitative (societal information) and quantitative (physical information and socio-economic information). The project will focus on the development of models to assimilate global data (e.g. from Earth observation or global socioeconomic databases), localization and domain decomposition techniques to assimilate existing local/in-situ data (e.g. field measurements of how certain types of fires burn and what they emit, country-specific socioeconomic information, data from surveys on how fire is perceived by local communities etc). The assimilated data will be used to: provide accurate estimation of the system (merging, cleaning and optimizing all the available data); understand human perceptions of fire (mainly assimilating and merging the available social media information); estimate optimal sensor positioning through the implementation of gaussian processes technologies. The project  will analyse existing palaeoenvironmental databases and fire modelling and will contribute to the advancement of a wider model of human-climate-fire interaction being developed by the Leverhulme Centre for Wildfires, Environment and Society.

Studentship Overview
The studentship will be supervised by Dr. Rossella Arcucci and co-supervised by Prof. Colin Prentice at Imperial College London.  Dr Arcucci’s research focuses on numerical and parallel techniques for accurate and efficient data assimilation by exploiting the power of machine learning models. Prof Prentice's research focuses on understanding how plants react to and interact with changes in climate and other aspects of the physical environment.

The student will be affiliated with two of the six Global Institutes of Imperial College London, created to address some of the most important issues facing the world today – the Data Science Institute (where the student will be based) and Grantham Institute- Climate Change and the Environment, both at Imperial’s South Kensington campus. The Data Science Institute hosts researchers who use data science techniques for applications in various fields, from healthcare to business, from environment to transport. The Grantham Institute is a leading authority on climate and environmental science, providing a vital global centre of excellence for research and education on climate change. The student will be aligned with the Science and Solutions for a Changing Planet Doctoral Training Partnership (SSCP DTP) based at the Grantham Institute and will take part in the multidisciplinary training programme that the SSCP DTP provides to its PhD researchers.

The student will also join a vibrant interdisciplinary research community in the Leverhulme Centre for Wildfires, Environment and Society, which includes staff and PhD students from Imperial College London, King’s College London, the University of Reading and Royal Holloway, University of London, with a common vision of producing evidence-based understanding of the human-fire nexus that can help inform policy and practice.

How to apply
The applicant will have a good undergraduate degree (min 2.1) in environmental sciences or an allied field. They will either have, or be working towards, a Masters degree or equivalent in a relevant field. The successful candidate will have good quantitative skills and programming experience. They will have experience of writing to a high standard, and a willingness to work in interdisciplinary teams.

Applicants should submit:
i) A CV (max 2 A4 sides), including details of two academic references;
ii) A cover letter outlining their qualifications and interest in the studentship (max 2 A4 sides)

These should be sent by email to r.arcucci@imperial.ac.uk and c.prentice@imperial.ac.uk by 15^th June 2020 with “Leverhulme – Data Assimilation PhD” as the subject. Interviews will take place, virtually, at the end of June/ early July 2020.

For further information on the project, please contact r.arcucci@imperial.ac.uk

Funding Notes

The studentship will be funded at £17,285 stipend per annum (including London allowance) paid for four years. The studentship will cover UK/EU fees for three years, and writing-up fees for the final year. There will be support funding for fieldwork and conference attendance. The studentship will start in October 2020.

In the group of Professor Hugh Brady, at the Department of Life Sciences, Imperial College London

 Informal inquiries are welcome and should be sent to Professor Hugh Brady (h.brady@imperial.ac.uk)

Cell therapy is a prime focus for biopharma R&D investment. Natural Killer (NK) cell immunotherapy is such an approach. NK cell therapy has been hampered by two problems:

1. Inability to scale-up production of highly cytotoxic human NK cells
2. Inability to engineer more active NK cells

We have shown that the E4bp4/Nfil3 transcription factor is the critical regulator of NK cell production. We have recently identified small molecules that activate E4bp4 gene expression. The project will:

1. Explore the mechanism of action of the small molecules on the E4bp4 gene.

2. Optimise the use of these small molecules to speed up and maximize production of highly cytotoxic human NK cells in culture from human cord blood stem cells, a technique well-established in our laboratory.

3. Use lentiviral-delivered sgRNA and CRISPR-Cas9 to delete discrete genes important for human NK cell function. Lentiviral-mediated gene deletion technique is well established in our laboratory.

The project will integrate the small molecule work to produce large amounts of engineered human NK cells with studying the function of these cells and how their biological processes are altered by each gene deletion. This student will receive training in human blood stem cell isolation and culture, lentiviral transduction, molecular cloning, flow cytometry, study of epigenetic regulation using ChIP; cell biology techniques and; immunological functional testing.

References:

Gascoyne D. et al., The basic leucine zipper transcription factor E4BP4 is essential for NK cell development. Nature Immunology 2009 10:1118-1124. DOI: 10.1038/ni.1787

Kostrzewski T. et al., Multiple levels of control determine how E4bp4/Nfil3 regulates NK cell development. Journal of Immunology 2018 200:1370-1381. DOI: 10.4049/jimmunol.1700981

Male V. et al., The transcription factor E4bp4/Nfil3 controls commitment to the NK lineage and directly regulates Eomes and Id2 expression. Journal of Experimental Medicine 2014 211:635-642. DOI: 10.1084/jem.20132398

We wish to widen participation and therefore we strongly encourage applications from individuals who completed their Bachelors and/or Masters degrees at non-Russell group Universities. We are particularly keen to get applications from underrepresented groups (eg. BAME candidates). For candidates with a non-Russell group background we are offering an online Q&A session where we will provide advice and support for application and interview process for a PhD position. Candidates should contact Rozan Hamilton-Nixon (r.hamilton-nixon@imperial.ac.uk) who will provide details on how to access this session. For information on the specific advertised projects please contact the relevant supervisor (see below). For additional information on the general support provided to PhD students at Imperial College and within the Department of Life Sciences contact Rozan Hamilton-Nixon (r.hamilton-nixon@imperial.ac.uk).

Funding and Eligibility: The studentships will cover UK/EU tuition fees of £4,407pa and will provide an annual tax -free maintenance stipend of £17,285, in 12 monthly instalments. Studentships are expected to last for 36 months, subject to satisfactory progress. A BSc in biological, or related, sciences is required at Upper Second Class level or better and candidates with a Masters degree, in addition to the BSc, might be given preference. Candidates must be either UK or EU nationals, resident in the UK for at least 3 years prior to the commencement of the studentships. Non UK/EU nationals are not eligible.

How to apply: Applications should include a full CV, names, addresses and contact details of two academic referees, and a cover letter (500 words max) describing why you want to do a PhD and the chosen PhD project in particular. Applications should be submitted by email to Rozan Hamilton-Nixon (r.hamilton-nixon@imperial.ac.uk).

Deadline for applications: 12 noon 29^th May 2020.

In the group of Dr Morgan Beeby, at the Department of Life Sciences, Imperial College London

Informal inquiries are welcome and should be sent to Dr Morgan Beeby (m.beeby@imperial.ac.uk)

This project will use electron cryo-tomography to determine 3-D structures of bacterial flagellar motors to sufficient resolutions to see the locations of motor proteins, and use bacterial genetics to understand their mechanism. The project has two objectives: determine the structure of the flagellar stator (the motor proteins that drive rotation) and determine the structure of the flagellar rotor (the passive proteins that are rotated by the stator motor proteins). The work builds on a series of recent strong preliminary results from the lab.

The student will first determine the structure of the stator component of Salmonella flagellar motors using electron cryo-tomography. Stator complexes assemble as a peptidoglycan-anchored ring to form the stator, spanning the membrane to contact the cytoplasmic rotor. Determining the locations of the stator complexes relative to the rotor will be an asset in understanding torque generation. Building on previous work the student will clarify the structure and occupancy of the stator complexes, with the ultimate goal of visualizing different conformations representing a ‘power stroke’ for torque generation. The student will subsequently determine the structure of the flagellar rotors using electron cryo-tomography to ~10 Å resolution using a recent genetic breakthrough we have made to greatly increase the sample yield for unprecedented resolutions. 

This work draws on long-term established collaborations and access to world-class electron microscopy facilities at the Crick Institute via my Crick Satellite Group position and has implications for targeted drug design and synthetic co-optation of the flagellar motor for our own microfluidic, cargo delivery, and as-yet-unforeseen applications.

References:

Beeby, Morgan, Josie L. Ferreira, Patrick Tripp, Sonja-Verena Albers, and David R. Mitchell. ‘Propulsive Nanomachines: The Convergent Evolution of Archaella, Flagella, and Cilia’. FEMS Microbiology Reviews, March 2020. https://doi.org/10.1093/femsre/fuaa006.

Chaban, Bonnie, Izaak Coleman, and Morgan Beeby. ‘Evolution of Higher Torque in Campylobacter- Type Bacterial Flagellar Motors’. Scientific Reports 8, no. 1 (8 January 2018): 97. https://doi.org/10.1038/s41598-017-18115-1.

Rossmann, F. M., and M. Beeby. ‘Insights into the Evolution of Bacterial Flagellar Motors from High-Throughput in Situ Electron Cryotomography and Subtomogram Averaging’. Acta Crystallographica Section D: Structural Biology 74, no. 6 (1 June 2018). https://doi.org/10.1107/S2059798318007945.

We wish to widen participation and therefore we strongly encourage applications from individuals who completed their Bachelors and/or Masters degrees at non-Russell group Universities. We are particularly keen to get applications from underrepresented groups (eg. BAME candidates). For candidates with a non-Russell group background we are offering an online Q&A session where we will provide advice and support for application and interview process for a PhD position. Candidates should contact Rozan Hamilton-Nixon (r.hamilton-nixon@imperial.ac.uk) who will provide details on how to access this session. For information on the specific advertised projects please contact the relevant supervisor (see below). For additional information on the general support provided to PhD students at Imperial College and within the Department of Life Sciences contact Rozan Hamilton-Nixon (r.hamilton-nixon@imperial.ac.uk).

Funding and Eligibility: The studentships will cover UK/EU tuition fees of £4,407pa and will provide an annual tax -free maintenance stipend of £17,285, in 12 monthly instalments. Studentships are expected to last for 36 months, subject to satisfactory progress. A BSc in biological, or related, sciences is required at Upper Second Class level or better and candidates with a Masters degree, in addition to the BSc, might be given preference. Candidates must be either UK or EU nationals, resident in the UK for at least 3 years prior to the commencement of the studentships. Non UK/EU nationals are not eligible.

How to apply: Applications should include a full CV, names, addresses and contact details of two academic referees, and a cover letter (500 words max) describing why you want to do a PhD and the chosen PhD project in particular. Applications should be submitted by email to Rozan Hamilton-Nixon (r.hamilton-nixon@imperial.ac.uk).

Deadline for applications: 12 noon 29^th May 2020.

In the group of Dr James Murray, at the Department of Life Sciences, Imperial College London

Informal inquiries are welcome and should be sent to Dr James Murray (j.w.murray@imperial.ac.uk)

The Calvin cycle is the metabolic pathway for carbon fixation in plants, algae and cyanobacteria. A key mechanism of Calvin cycle regulation is via the redox state. In the light, the cytoplasm becomes reduced as photosystem I produces reduced ferredoxin. In the dark, the cytoplasm becomes oxidising. This redox change regulates several key Calvin cycle enzymes, including glyceraldehyde phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK) [1]. Under oxidising conditions, GAPDH and PRK form a complex with a small regulatory protein, CP12, triggered by the formation of disulfide bonds in CP12. A recent PhD student solved the crystal structure of CP12 in complex with GAPDH, and the cryoEM structure of the GAPDH-CP12-PRK complex from a thermophilic cyanobacterium [2].

We wish to extend this structural knowledge through the further structure-function studies, including the X-ray or cryoEM complex structure from crop plants such as rice and wheat, and with different plant isoforms of CP12. We also wish to probe via mutagenesis and biochemical experiments the structural basis of complex formation – such as the unknown function of the conserved C-terminal disulfide bond in PRK.

It is likely that plants are conservative in their regulation of photosynthesis, and that crops under relatively stress-free cultivation could be engineered to fix more carbon. Structural understanding of this complex will enable its formation to be modulated, and finer control of carbon fixation.  

Figure: The GAPDH(blue)-CP12(magenta)-PRK (orange) complex, solved at 3.7 Å by cryoEM.

Techniques: biochemistry, molecular biology, X-ray crystallography,   electron cryomicroscopy, see [3] for recent Murray lab papers.H(blue)-CP12(magenta)-PRK (orange) complex, solved at 3.7 Å by cryoEM.

References

[1]         Gontero, B.; Maberly, S. C. An Intrinsically Disordered Protein, CP12: Jack of All Trades and Master of the Calvin Cycle. Biochemical Society transactions 2012, 40 (5), 995–999. https://doi.org/10.1042/bst20120097.

[2]         McFarlane, C. R.; Shah, N. R.; Kabasakal, B. V.; Echeverria, B.; Cotton, C. A. R.; Bubeck, D.; Murray, J. W. Structural Basis of Light-Induced Redox Regulation in the Calvin–Benson Cycle in Cyanobacteria. PNAS 2019, 201906722. https://doi.org/10.1073/pnas.1906722116.

[3] https://scholar.google.com/citations?user=R0oSsA8AAAAJ&hl=en

We wish to widen participation and therefore we strongly encourage applications from individuals who completed their Bachelors and/or Masters degrees at non-Russell group Universities. We are particularly keen to get applications from underrepresented groups (eg. BAME candidates). For candidates with a non-Russell group background we are offering an online Q&A session where we will provide advice and support for application and interview process for a PhD position. Candidates should contact Rozan Hamilton-Nixon (r.hamilton-nixon@imperial.ac.uk) who will provide details on how to access this session. For information on the specific advertised projects please contact the relevant supervisor (see below). For additional information on the general support provided to PhD students at Imperial College and within the Department of Life Sciences contact Rozan Hamilton-Nixon (r.hamilton-nixon@imperial.ac.uk).

Funding and Eligibility: The studentships will cover UK/EU tuition fees of £4,407pa and will provide an annual tax -free maintenance stipend of £17,285, in 12 monthly instalments. Studentships are expected to last for 36 months, subject to satisfactory progress. A BSc in biological, or related, sciences is required at Upper Second Class level or better and candidates with a Masters degree, in addition to the BSc, might be given preference. Candidates must be either UK or EU nationals, resident in the UK for at least 3 years prior to the commencement of the studentships. Non UK/EU nationals are not eligible.

How to apply: Applications should include a full CV, names, addresses and contact details of two academic referees, and a cover letter (500 words max) describing why you want to do a PhD and the chosen PhD project in particular. Applications should be submitted by email to Rozan Hamilton-Nixon (r.hamilton-nixon@imperial.ac.uk).

Deadline for applications: 12 noon 29^th May 2020.

A 3 year EPSRC-funded PhD studentship is offered in the group of Professor Jasper van Thor at Imperial College London in the area of ultrafast X-ray Free Electron Laser (XFEL) and ultrafast laser science. XFEL’s are revolutionising structural biology to add the time domain to atomic resolution information, with a time resolution currently possible of ~100 femtoseconds using the pump-probe technique.

A studentship is offered that will provide training in the specialised and emerging technique of ultrafast time resolved Serial Femtosecond Crystallography at X-ray Free Electron Lasers. These are pump-probe experiments applied to the ‘Serial Femtosecond Crystallography’ method at Angstrom wavelength, available at LCLS (USA), SACLA (Japan), European XFEL (Germany) and additionally PAL-XFEL (Korea) and SwissFEL (Switzerland). In the home laboratory the research will also involve ultrafast spectroscopy of oriented single protein crystals to measure and control femtosecond reactions. In collaboration with the Jon Marangos group in the Physics Department there will be additional opportunities to join X-ray Free Electron Laser experiments to gain experience with experiments relevant to atomic, molecular and optical physics

Eligibility and how to apply:

Applicants should have a BSc degree at 2:1 level or better, either in Physics or in Chemistry or Biochemistry and a relevant Masters degree in Physical Sciences or Biochemistry, ideally Structural Biology. Preference will be given to applicants with proven experience in coding, including Python, and who are comfortable with data handling and computation and have experimental experience. Life Science graduates will need to demonstrate ability and experience in computing and Physical Sciences methodologies as well as have excellent Mathematics skills.

Only UK and EU nationals 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.

Initial applications should include a full CV, names, addresses and contact details of two academic referees, and a personal statement (500 words max). These should be submitted to Jasper van Thor (j.vanthor@imperial.ac.uk)

Enquiries may also be made to Jasper van Thor (j.vanthor@imperial.ac.uk)

Deadline for submission of applications is 5th June 2020.

Selected References

van Thor JJ (2019) Advances and opportunities in ultrafast X-ray crystallography and ultrafast structural optical crystallography of nuclear and electronic protein dynamics, Structural Dynamics, Vol: 6, 050901

Hutchison CDM, van Thor JJ (2019) Optical Control, selection and analysis of population dynamics in Ultrafast protein X-ray crystallography, Philosophical Transactions A: Mathematical, Physical and Engineering Sciences, Vol: 377, Pages: 20170474-20170474

Sanchez-Gonzalez A, Johnson AS, Fitzpatrick A, Hutchison CDM, Fare C, Cordon-Preciado V, Dorlhiac G, Ferreira JL, Morgan RM, Marangos JP, Owada S, Nakane T, Tanaka R, Tono K, Iwata S, van Thor JJ (2017), Coincidence timing of femtosecond optical pulses in an X-ray free electron laser, Journal of Applied Physics, Vol: 122, ISSN: 0021-8979. doi.org/10.1063/1.5012749

Hutchison CDM, Cordon-Preciado V, Morgan RML, Nakane T, Ferreira J, Dorlhiac G, Sanchez-Gonzalez A, Johnson AS, Fitzpatrick A, Fare C, Marangos JP, Yoon CH, Hunter MS, DePonte DP, Boutet S, Owada S, Tanaka R, Tono K, Iwata S, van Thor JJ (2017) X-ray Free Electron Laser Determination of Crystal Structures of Dark and Light States of a Reversibly Photoswitching Fluorescent Protein at Room Temperature. Int. J. Mol. Sci. 18(9), 1918; doi:10.3390/ijms18091918

Pande K, Hutchison CDM, Groenhof G, Aquila A, Robinson JS, Tenboer J, Basu S, Boutet S, DePonte DP, Liang M, White TA, Zatsepin NA, Yefanov O, Morozov D, Oberthuer D, Gati C, Subramanian G, James D, Zhao Y, Koralek J, Brayshaw J, Kupitz C, Conrad C, Roy-Chowdhury S, Coe JD, Metz M, Xavier PL, Grant TD, Koglin JE, Ketawala G, Fromme R, Srajer V, Henning R, Spence JCH, Ourmazd A, Schwander P, Weierstall U, Frank M, Fromme P, Barty A, Chapman HN, Moffat K, van Thor JJ, Schmidt M (2016), Femtosecond structural dynamics drives the trans/cis isomerization in photoactive yellow protein, SCIENCE, Vol: 352, Pages: 725-729

Hutchison CDM, Kaucikas M, Tenboer J, Kupitz C, Moffat K, Schmidt M, van Thor JJ (2016) Photocycle populations with femtosecond excitation of crystalline photoactive yellow protein, Chemical Physics Letters, Vol: 654, Pages: 63-71

C. Hutchison and J.J. van Thor (2016) Populations and coherence in femtosecond time resolved X-ray crystallography of the Photoactive Yellow Protein. Int Rev Phys Chem. 36, 117-143

van Thor JJ, Madsen A, (2015), A split-beam probe-pump-probe scheme for femtosecond time resolved protein X-ray crystallography, Structural Dynamics, Vol: 2, Pages: 014102-014102.

In the group of Dr Jie Song, at the Department of Life Sciences, Imperial College London

Address: South Kensington Campus, London SW7 2AZ, UK

This PhD project aims to characterise Polycomb-based epigenetic regulation in the model plant Arabidopsis. Throughout development, Polycomb silencing acts in a strictly controlled manner, spatially –with confined regions being silenced, and temporally –target loci being silenced in specific periods in the life cycle. The PhD student will investigate how the chromatin modifying complex Polycomb is targeted to specific loci in order to give rise to such distinct gene silencing patterns.

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

How to apply:

Please email Dr Song (j.song@imperial.ac.uk) and include in your application:

• A cover letter
• Your CV 
• Your transcripts
• Three references sent directly from the referees

Applications will be considered as they are received and the position will remain open until filled.  

General entry requirements for graduate studies at Imperial College London can be found at http://www.imperial.ac.uk/study/pg/apply/requirements/.

 Funding notes:

This is a 4-year PhD Studentship, including home fees and a standard stipend of £17,009, funded jointly by the Royal Society and the Department of Life Sciences, Imperial College London.

International applicants: please note that the fees paid are at UK/EU level. Any shortage in fees will need to be met by the applicant from external sources.

Hosted by Dr. Tiago Costa:  Department of Life Sciences

Key words: cryo-electron microscopy, type IV secretion system, macromolecular complex, protein- DNA injection, antibiotic resistance.

Overview: Type IV secretion systems (T4SS) are ubiquitous nanomachines that assemble at the bacterial inner and outer membranes to orchestrate the delivery of proteins and DNA into bacterial and eukaryotic cell targets. T4SSs are not only the crucial drivers of antibiotic resistance spreading during bacterial conjugation, they are also capable of secreting toxins that are lethal to other bacteria and human cells. T4SSs can be exploited as drug targets against antibiotic resistance spreading and bacterial infectious diseases.

This exciting PhD project aims to unveil the structural and functional details underlying the mechanism of DNA and toxins secretion by T4SSs. The project will use single particle cryo-electron microscopy to obtain near-atomic details that elucidate how substrates are recruited, transported and secreted to target cells. This is a multidisciplinary project that involves the biochemical isolation and characterization of large membrane complexes combined with cutting-edge single particle cryo-EM.

How to apply: Please send your CV (including contact details of two referees) with a cover letter describing why you are suitable for this PhD studentship and interested in the project to Dr Tiago Costa t.costa@imperial.ac.uk.

About the candidate: Applicants should have a strong background in protein biochemistry. Some preliminary experience with cryo-electron microscopy is desirable but not essential.

Candidates must have or expected to gain a First class or Upper Second class Honours degree in Biological Sciences (or other related appropriate science subject).  Preference will be given to candidates with a Master’s degree or equivalent research experience in a relevant subject area.

Due to funding availability, only Home/EU students can be considered for this studentship.

Funding: The studentship is funded by the National Institute of Health (NIH-USA) and covers Home/EU tuition fees and a stipend of £18,000 per annum for 3.5 years.

The project will start on October 2020 or anytime after May 2020 depending on candidate availability.

References:

1.            Williams, A.H., Redzej, A., Rolhion, N., Costa, T.R.D., Rifflet, A., Waksman, G., and Cossart, P. (2019). The cryo-electron microscopy supramolecular structure of the bacterial stressosome unveils its mechanism of activation. Nature communications 10, 3005.

2.            Sgro, G.G., Costa, T.R.D., Cenens, W., Souza, D.P., Cassago, A., Coutinho de Oliveira, L., Salinas, R.K., Portugal, R.V., Farah, C.S., and Waksman, G. (2018). Cryo-EM structure of the bacteria-killing type IV secretion system core complex from Xanthomonas citri. Nat Microbiol 3, 1429-1440.

3.            Galan, J.E., and Waksman, G. (2018). Protein-Injection Machines in Bacteria. Cell 172, 1306-1318.

4.            Costa, T.R., Ilangovan, A., Ukleja, M., Redzej, A., Santini, J.M., Smith, T.K., Egelman, E.H., and Waksman,

G. (2016). Structure of the Bacterial Sex F Pilus Reveals an Assembly of a Stoichiometric Protein- Phospholipid Complex. Cell 166, 1436-1444 e1410.

5.            Costa, T.R., Felisberto-Rodrigues, C., Meir, A., Prevost, M.S., Redzej, A., Trokter, M., and Waksman, G. (2015). Secretion systems in Gram-negative bacteria: structural and mechanistic insights. Nature reviews Microbiology 13, 343-359.

Closing date: 10th January of 2020