About the Project
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 goes significantly beyond the state-of-the-art. Instead of blocking a target protein with conventional inhibitors, we are now designing and studying “tailored” molecules, bivalent conceptually and in function, that bring proteins together by forming stable and cooperative ternary complexes. We have shown that this key ternary recognition feature allows for fast and effective induce proximity-driven chemistries, specifically 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 trigger 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; structural biology and biophysics 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 into relevant cellular systems – for example cancer cells sensitive to the knockdown of the protein target in question. Our science takes advantage of latest technologies and vast expertise available at the School of Life Sciences e.g. within the FingerPrint Proteomics Facility and the Drug Discovery Unit that we have access to. We collaborate with several research groups within the School, including the Divisions of MRC-PPU, GRE, and CSI, to deploy our bivalent molecules to interrogate the biology of targets of interest and to dissect the functional consequences of disrupting the signaling networks in which they are involved.
A one-year Master project would typically fit as part of on-going projects and research interests 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.
Please see our website for further details and how to apply - https://www.dundee.ac.uk/study/pgr/life-sciences-msc-research/
Gadd, M. S. et al. (2017) Nat. Chem. Biol. 13, 514-521.
Maniaci, C. et al. (2017) Nat. Commun. 8, 830.
Hughes, S.J., and Ciulli, A. (2017) Essays in Biochem. 61, 505-516.
Maniaci, C., and Ciulli, A. (2019) Curr Opin Chem. Biol. 52, 145-156.
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