We always welcome considering interested and motivated students to embark on their PhD in our laboratory. You are encouraged to familiarize yourself with the PhD Programme hosted within our School of Life Sciences at Dundee. If you want to learn more about our research and are considering joining our group for a PhD starting from 2019, do not hesitate to contact Alessio directly by e-mail.
Available Openings (New: January-February 2021)
Project 1: EASTBIO: Bifunctional small molecules beyond PROTACs: Proximity-inducing new downstream chemistries to rewire cell signaling
Proteolysis targeting chimeras (PROTACs) are a popular class of bifunctional molecules that simultaneously engage a target protein on one end and an E3 ubiquitin ligase on the other end, forming a ternary complex that facilitates the rapid ubiquitylation and subsequent degradation of the target protein. With this Studentship we seek to harness the principles of the mode of action of PROTACs via the ternary complex to develop and characterize a novel class of heterobifunctional molecules that bring the target protein into proximity to enzymes of a different class from E3 ligases – namely enzymes that natively regulate phosphorylation of substrate proteins. These molecules have the potential to expand the ways in which undruggable proteins can be targeted for proximity-induced chemistry beyond PROTACs, thereby significantly advance research and therapy.
For more information on the project, please read here.
Deadline to submit applications: Wednesday, January 06, 2021.
Apply now here!
Project 2: Chinese Scholarship Council: Structural and Mechanistic Chemical Biology of Degraders Mode of Actions
Pioneering discoveries from the Ciulli Laboratory and others have contributed to the establishment of a new modality of chemical intervention into biological system, whereby small molecules can now degrade proteins rather than inhibiting them. Such degrader molecules, also known as PROTACs, can recruit target proteins to E3 ubiquitin ligases to induce target ubiquitination and degradation.
Our research in this area is conducted within the auspices of a new Centre for Targeted Protein Degradation at Dundee. It takes a multidisciplinary approach including:
1) Organic and medicinal chemistry and computational tools to design and achieve desired molecules;
2) Structural biology and biophysics to study binary and ternary complexes in solution and reveal their structural and dynamic interactions; and
3) 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, or model cell lines suitable for biological investigation of specific signalling pathways.
Potential projects in this area range from:
a) Biological and functional studies in cells of potent and selective PROTACs for proteins of interest to us and/or collaborators, and evaluation of their potential as drug targets, particularly in cancer.
b) Identification, and biochemical, biophysical and structural studies of new E3 ubiquitin ligases for PROTACs
c) Fundamental structural and mechanistic studies of novel degrader modalities, e.g. homo-PROTACs and our recently described trivalent-PROTACs
The project can be tailored to the student specific interests and motivations.
For more information on the project, please read here.
Deadline to submit applications: Monday, February 08, 2021.
In order to be eligible for this award applicants must be a Chinese national. Apply now here!
MSC by Research Programme - Bringing 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 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/
Applications can also be submitted via Find-a-PhD.com
References
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.
Please keep checking these pages for update, and feel free to contact me for informal enquiries