Liquid-liquid phase separation is emerging as a crucial phenomenon in fundamental cell processes (https://doi.org/10.1126/science.aaf4382). Many eukaryotes exhibit liquid condensates, however, their function in bacteria remains less clear. Following our exciting recent findings ((Pu et al Mol Cell 2019 https://doi.org/10.1016/j.molcel.2018.10.022, Jin et al Science Adv 2021 https://doi.org/10.1101/2021.06.24.449778), that show how bacteria use protein droplets to survive stresses such as antibiotics, we will develop new strains of E. coli expressing fluorescent reporters to proteins involved in forming a liquid droplet called an aggresome, an enigmatic membraneless organelle, and use high-resolution optical microscopy to observe these in live bacteria, to uncover the mechanistic properties of their formation and dissolution, and undercover their role in cell stress. The Leake Lab, in collaboration with Hawkins and McLeish at the University of York and Fan Bai at Peking University, Beijing, are looking to recruit a highly motivated and dedicated student to undertake a PhD that will combine cutting-edge bacterial genetics, super-resolution microscopy and mathematical modelling to give us an unprecedented understanding of the structure and function of the bacterial aggresome. The successful PhD candidate will:
1) Generate fluorescently labelled aggresome factors to define the spatiotemporal dynamics of aggresome biogenesis in real time.
2) Track formation of aggresomes in live cells under conditions of stress using single-molecule microscopy established in the Leake Lab (https://doi.org/10.1126/science.1185757https://doi.org/10.1126/science.1227126).
3) Analyse the disaggregation aggresomes as cells recover from dormancy to determine whether disassembled proteins are reused at their functional site or are degraded.
4) Work with theoretical modeling predictions to enable new insights into how aggresomes form and dissolve.
We are interested to hear from students interested in one or more of the following areas: molecular biology, microbiology, biophysics, microscopy, biomathematics.
Supervisor/collaborator labs: Mark Leake (http://single-molecule-biophysics.org/), Michelle Hawkins (https://www.york.ac.uk/biology/our-staff/dr-michelle-hawkins/), Tom McLeish (https://www.york.ac.uk/physics/research/physics-of-life/theoretical-biological/), Fan Bai (https://icg.pku.edu.cn/en/research/faculty/511404.htm).
The WR DTP and the University of York are committed to recruiting future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and we have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.
Entry Requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with backgrounds in any biological, chemical, and/or physical science, or students with mathematical backgrounds who are interested in using their skills in addressing biological questions.
Programme: PhD in Mechanistic Biology (4 years)
Start Date: 1st October 2022 (the student will be affiliated with the Department of Biology)
Shortlisted candidates will be interviewed in mid February 2022
Continue with Facebook
