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PhD project: Control of protein aggregation by liquid-liquid phase separation


   Department of Physics and Astronomy

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  Dr Thomas Michaels  No more applications being accepted  Funded PhD Project (UK Students Only)

London United Kingdom Bioengineering Biophysics Cell Biology Chemical Physics Computational Chemistry Computational Physics Molecular Biology Nanotechnology Physical Chemistry Theoretical Physics

About the Project

The newly established Michaels’ lab at University College London (UCL) is looking to recruit an exceptional and highly motivated student for an exciting and fully funded PhD project in theoretical biophysics at the interface of physics, biology and biomedicine. The project seeks to use a combination of analytical theory, computer simulations and methods of artificial intelligence and control theory to understand the fundamental mechanisms by which phase-separated liquid condensates regulate the aggregation of proteins into functional/dysfunctional assemblies. 

Brief project description: Reversible aggregation of proteins into complex assemblies is the driving force by which nature generates the basic machinery of life (e.g. actin filaments and tubulin microtubules). Uncontrolled irreversible aggregation, however, is linked to numerous medical conditions, including Alzheimer’s and Parkinson’s diseases. Understanding the mechanisms underlying spatial and temporal control of such reactions is therefore a fundamental goal of molecular biology, not least because it opens up new opportunities to reprogram pathological behaviour linked to disease.

One attractive and emerging control strategy is to use so called biomolecular condensates or liquid organelles, which have recently attracted tremendous interest due to their key role in spatially regulating biochemical activities within living cells. Unlike traditional membrane-bound organelles, these biomolecular condensates do not possess a membrane and form by liquid-liquid phase separation of proteins in the cytoplasm. Here we are looking to combine ideas from theoretical biophysics, control theory and machine learning to uncover the fundamental physical mechanisms by which phase-separated biomolecular condensates control different classes of protein aggregation processes, which remains an open question in most cases. These include, but are not limited to, control of nucleating biopolymers and protein fibrils, assembly of tight junction, and generation of mechanical forces.

This approach will enable us to identify fundamental control rules behind existing biological aggregating systems, as well as to propose novel rational strategies for drug discovery against aberrant aggregation. The project involves exciting international collaborations with several experimental and theoretical groups.

About us: The Michaels’ lab at UCL develops theoretical models to unravel fundamental control principles of biochemical processes in living systems. The research group, led by Dr Thomas Michaels, is based at the UCL Department of Physics and Astronomy and the Institute for the Physics of Living Systems (IPLS), in central London. IPLS is a lively cross-faculty institute with a mission to promote research at the interface of physical and life sciences.

Eligibility: Applicants must be UK nationals or have EU settled status or indefinite leave to remain under the EU Settlement Scheme. The successful applicant should have (or expect to achieve) at least a UK upper second class MSci or Master’s degree or equivalent in Physics, Mathematics, Chemistry, Engineering, or a relevant subject. The candidate should possess high level of self-motivation and enthusiasm, strong communication skills and a demonstrated experience with quantitative mathematical modelling. Some experience in programming is desired but not required. No prior knowledge of biology or biophysics is necessary. 

How to apply: To apply, candidates are requested to follow the application procedure on https://www.ucl.ac.uk/physics-astronomy/study/phd and to send a PDF copy of their application to Dr. Thomas Michaels ([Email Address Removed]), who will very happily welcome informal inquiries on this project. Electronic applications are therefore via https://www.ucl.ac.uk/prospective-students/graduate/apply The application forms ask for CV details, academic transcripts, contact details of two referees, and a personal statement.

Application deadline: The evaluation of applications will begin after 26/02/2021 and will run until the position is filled. Interviews will be held in March 2021.


References

Michaels TCT, et al, Optimal control strategies for inhibition of protein aggregation, Proceedings of the National Academy of Sciences 116, 14593 (2019).
Weber CA, Michaels TCT, et al, Spatial control of irreversible protein aggregation, Elife 8, e42315 (2019).
Michaels TCT, et al, Dynamics of oligomer populations formed during the aggregation of Alzheimer’s Aβ42 peptide, Nature Chemistry 12, 445 (2020).
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