Potential Supervisors within this theme
Prof Alessio Ciulli
Research from us and others over the past decade have contributed to the advent of a new modality of chemical and drug intervention to study biology and cure disease. Instead of blocking a target protein as conventionally done with inhibitors, we are designing “tailored” bifunctional molecules that bring a target protein to an E3 ubiquitin ligase. We are beginning to understand the rules and principles of how to design and study this new class of molecules and how to best investigate the profound biological consequences and attractive therapeutic potential of targeted protein degradation. 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, or model cell lines suitable for biological investigation of specific signalling pathways.
Prof Vicky Cowling
We investigate how formation of the mRNA cap is regulated in mammalian cells and the impact that this has on gene expression and cell function. We investigate the impact of mRNA cap regulation during embryonic stem cell differentiation and T cell activation. We work with the Dundee Drug Discovery Unit to investigate therapeutic targeting of the mRNA cap.
Prof David Gray
As Head of Biology within the Drug Discovery Unit (DDU),my role is to develop strategies for people, facilities, equipment and IT to allow the effective support of hit discovery, hits to leads and lead optimisation programs. We currently support two broad areas, these being neglected diseases (malaria, leishmania, sleeping sickness, TB and Chagas’ disease) and innovative targets; a portfolio to translate new biological findings from Dundee and beyond. We conduct assay development, small molecule screening and an extensive array of mechanism of action and other supporting biology to define and characterise small molecule tools suitable for use in primary biological research and drug discovery.
Prof Bill Hunter
Understanding the detailed chemical interactions between targets and small molecules allows us to advance ideas that will ultimately lead to more potent inhibitors designed to assist drug discovery or to generate reagents for further research. I have a long-term interest in targeting microbial pathogens, which present major health and veterinary problems in developing countries and more recently we are developing projects in the neurosciences area. The major technique applied in the laboratory is single crystal X-ray diffraction, a mix of physics, chemistry and biochemistry, and this is aided by additional physical chemistry, molecular screening and biological techniques. Aspects of computational modeling assist our studies and productive collaborations with synthetic chemists provide valued reagents for study.
Dr Mattie Pawlowic
Our research focus is on Cryptosporidium, a waterborne parasite that can cause chronic diarrhoea, dehydration and malnutrition. We concentrate in two main areas: understanding the basic biology and biochemistry of Cryptosporidium, and drug discovery in collaboration with WCAIR and the Drug Discovery Unit (DDU). Developing new genetic tools to work with the parasite will help both aims. “Infection occurs through the oral ingestion of an oocyst. The wall of an oocyst is extremely protective and can withstand bleaching and chlorination. If we can unravel the structure of this wall we can develop drugs to interfere with the infection cycle,” explained Dr. Pawlowic. “Cryptosporidium is difficult to genetically manipulate and you cannot culture it continuously. At the University of Georgia, I used CRISPR to make the first genetic knockout of Cryptosporidium. Now we have the chance to use that technology in collaboration with drug discovery to develop new drugs.”
Prof Paul Wyatt
My aim as Head of the DDU is to develop translational research at Dundee by integrating my and other’s experience of Drug Discovery in the Pharma/Biotech sector with academic life-sciences research. My role in leading a high quality, multi-disciplinary drug discovery team is to identify leads to validate novel drug discovery targets in animal models of disease and where appropriate develop them into new treatments.