Five 1+3 PhD studentship opportunities at The Institute of Chemical Biology EPSRC Centre for Doctoral Training for October 2022 entry

All projects commence in October 2022 and provide a full scholarship for our four year 1+3 MRes in Chemical Biology and Bio-Entrepreneurship PhD training programme. Competition for ICB CDT studentships is high, ensuring that only the best applicants are awarded a place on the course.

Our programme is aimed at chemistry, physics, mathematics and engineering graduates who wish to learn how to apply their physical sciences skills to biological problems. Students from biological or medicinal backgrounds are usually not eligible. If in doubt, please contact us.

Our studentships are for 4 years, covering the fees and bursary (stipend) for a one-year MRes Chemical Biology and Bio-Entrepreneurship, followed by a three-year PhD, subject to passing the MRes. Please see the ICB CDT website for fee status eligibility information.

The entry requirement is a degree in the physical sciences with a minimum 2.1 or above (or equivalent).

To apply to one or more of these projects, please visit:

https://www.imperial.ac.uk/chemical-biology/cdt/studentships/latest-projects-2022-entry/

On this site, you will find further details on the ICB CDT, the available projects, instructions on how to apply and the link to our online admissions system.

Please contact Emma Pallett (e.pallett@imperial.ac.uk) should you have any queries.

Available projects

Joint Vertex Pharmaceuticals Ltd Oxford / ICB EPSRC CDT four year 1+3 MRes in Chemical Biology and Bio-Entrepreneurship PhD training programme

Photoactivatable molecular probes to study RNA-protein interactions

This project is co-sponsored by the Institute of Chemical Biology EPSRC Centre for Doctoral Training and Vertex Pharm. Ltd. Oxford.

Supervisors: Professor Ramon Vilar (Imperial); Dr Marco Di Antonio (Imperial); Professor Edward Tate (Imperial/Francis Crick); Dr David Hewings (Vertex)

Abstract:

Due to their rich structural diversity and broad range of biological functions, targeting RNA with small molecules is becoming an important strategy in drug discovery. Most cellular functions of RNA are controlled by proteins and dysregulation of these interactions can lead to a range of human diseases. Therefore, there is an increasing interest in efficient methods to identify proteins that bind to specific RNA structures. This project aims to develop a new class of molecular probe (based on small organic and/or metal-organic molecules) for the selective photolabeling of RNA-binding proteins. The new probes developed in this project will be applied to study repeat expansions in RNA structures, several of which are responsible for various neurological and neuromuscular diseases.

Simultaneous imaging of protein-protein and protein-membrane interactions using molecular rotors

Supervisors: Dr Marina Kuimova, Dr Anna Barnard, Professor Bernadette Byrne

Abstract:

Protein-protein interactions (PPIs) are integral to all biological processes, including those involved in disease pathways. However, methods to study and quantify the effect of targeting these interactions in real time and at a single cell level are currently lacking. This project will develop an exciting opportunity to use molecular rotors, environmentally sensitive fluorophores, to quantitatively detect the function of a PPI inhibitor as a large change in fluorescence lifetime. We will develop novel peptide-rotor conjugates as tools to study the Bcl-2 family of PPIs, key oncology targets. Additionally, inhibition of these PPIs is inexorably linked to permeabilisation of the mitochondrial outer membrane. By employing rotors with complementary emission properties, we will develop methods to study both PPI inhibition and membrane integrity simultaneously, offering unprecedented insight into these interlinked biological events.

 

DNA-based, microRNA-sensing artificial cells for diagnostics and therapeutics

Supervisors: Dr Lorenzo Di Michele, Professor Charlotte Bevan, Dr Sylvain Ladame

Abstract:

MicroRNAs (miRs) are frequently found to be deregulated in bodily fluids of cancer patients and have great potential for early-stage diagnosis. Surprisingly, there is currently no cancer diagnostic test based on miR detection. Here, we will apply DNA nanotechnology to build “artificial cells” for multiplexed detection and quantitation of cancer-related miRs in patient samples. The technology will be tested in vitro on miRs overexpressed in prostate cancer, and then with cancer-patient serum or plasma, potentially unlocking a new non-invasive diagnostic route for a disease where early detection is particularly critical. The biocompatible artificial cells will then be further engineered to release therapeutic payloads upon miR detection, thus laying the foundations for a future therapeutic platform where ACs could be deployed in vivo as a targeted, low-toxicity cancer treatment activated by local miR upregulation.

 

Understanding Amyloid Post-Translational Modification at the Nanoscale

Supervisors: Dr Francesco A. Aprile, Professor Ramon Vilar, Dr Liming Ying

Abstract:

Alzheimer’s disease is a fatal and incurable form of dementia, affecting 40 million people worldwide. Despite the high prevalence of Alzheimer’s disease, currently, there is no cure or biometric diagnostic test for it. Small aggregates of the amyloid-beta peptide, called oligomers, cause toxicity in Alzheimer’s disease, and are associated with the disease’s onset and progression. Increasing evidence suggest that post-translational modifications alter the propensity of amyloid-beta to aggregate. However, there is currently no information on the implications of such modifications for oligomers’ structure and mechanisms, as oligomers are too heterogeneous and sparse to be studied with standard methods. To overcome this challenge, we will deliver a novel analytical platform to study oligomers at the single-molecule level. We will combine ultra-sensitive antibody detection with super-resolution microscopy and rational drug design to determine how pathological post-translational modifications affect the structure, toxicity, and druggability of amyloid-beta oligomers. Our results will provide unprecedented information on key mechanisms of Alzheimer’s disease and open new clinical intervention.

 

Plug-and-play discovery of molecular glues: a new drug discovery paradigm

Supervisors: Professor Ed Tate, Dr Louise Walport and Dr Jemima Thomas (Imperial & Francis Crick Institute)

Abstract:

Bifunctional drugs and molecular glues are emerging as powerful drug modalities with the potential to transform treatment of currently intractable diseases by targeting so-called ‘undruggable’ proteins. However, development of new drugs in this space is held back by the lack of generally applicable strategies for their discovery. This project will establish and develop the first universal screening platform to identify novel molecular glues which recruit a specific protein of interest to any desired endogenous cellular effector system, based on unique chemistry applied to billion-member encoded libraries. Through induction of an effector-target protein complex, compounds will trigger catalytic and versatile modulation of protein function, for example by inducing or removing a specific PTM, or by rewiring protein trafficking or signalling complexes, with profound consequences for chemical probe discovery and future therapeutics. This project would ideally suit a student with a strong chemistry or chemical biology background, with a passion for enabling new paradigms in drug discovery, and enthusiasm for learning and applying a diverse range of modern chemical biology approaches, from organic synthesis to molecular genetics, protein biochemistry, and cell biology.

 

Applicants need to apply through the Imperial College Gateway, via https://www.imperial.ac.uk/chemical-biology/cdt/studentships/how-to-apply/

 

 

 

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