MSc by Research: Glueing proteins together with small molecules

Recent advances from the Ciulli Lab and others have contributed to the establishment of a game-changing new modality of chemical intervention into biological system – one that moves beyond the state-of-the-art. Instead of blocking a target protein with conventional inhibitors, we are now designing and studying “tailored” molecules, multi-specific in concept and function, that bring two or more proteins together by forming a ternary (or higher order) complex. We have shown that specific molecular recognition features of such ternary complexes, such as their cooperativity and thermodynamic and kinetic stability, are a key feature of their “molecular glue” activity, and drive fast and effective induce proximity-driven chemistries. For degrader molecules that co-opt E3 ligases to target protein, this specifically relates to protein ubiquitylation and subsequent proteasomal degradation. We are beginning to understand the rules of how to design and study this new class of molecules in order to best re-wire specific downstream signaling events, with profound biological consequences and attractive therapeutic potential. 

Our research in this area takes a multidisciplinary approach including organic and medicinal chemistry and computational tools to design and achieve desired molecules;  biophysics and structural biology, including the use of cryo-electron microscopy, to study binary and ternary complexes in solution and reveal their structural and dynamic interactions; and chemical biology, biochemistry, proteomics and cell biology to study the cellular impact of our small molecules in relevant cellular systems – for example cancer cells sensitive to the knockdown or other modification of the protein target in question. Our science takes advantage of latest technologies and vast expertise available within our newly opened Centre for Targeted Protein Degradation (CeTPD) and within the wider School of Life Sciences e.g. the FingerPrint Proteomics and Cryo-EM Facilities. We collaborate with several research groups within the School, including the Divisions of MRC-PPU, MCDB and CSI, amongst others, to deploy our molecules to interrogate the biology of targets of interest and to dissect the functional consequences of selectively disrupting or augmenting the signaling networks in which they are involved. 

A one-year Master project would typically fit as part of an on-going project and research interest of the Lab. Importantly; it can be tailored to the student specific interests and motivations. If you are interested in joining the lab and contributing to our science in this exciting new area, to learn more about our work and to discuss potential opportunities, do not hesitate to get in touch with Alessio (a.ciulli@dundee.ac.uk). 

Please see our website for further details on the programme:

Life Sciences MSc by Research MSc by Research (Postgraduate) : Study : University of Dundee

Please note before submitting your application that you must list your top three project choices in the Research Proposal section of the application form.

You apply for this course using our Direct Application System. Once you've signed up for an account you'll be asked to search for a course.

https://www.dundee.ac.uk/study/pgr/research-areas/life-sciences/

To find Life Science MSc by Research you should select the following options:

· Course type: Research Postgraduate

· Keyword: Life

When you complete your form, you should include your top 3 project choices, 2 letters of reference, uploaded under "Other Information" > "Supporting documents" and a personal statement. Failure to do so will delay your application.

Please note when submitting an application, please note our intake deadlines on the ‘how to apply’ section of our website