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 and a relevant Masters degree in Physical Sciences ideally in ultrafast optics or laser science. 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. In exceptional cases Life Science graduates will be considered, but 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 17^th February 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