Design, synthesis and evaluation of novel therapeutics for type 2 diabetes.
Diabetes (specifically type 2) has been described as the greatest pandemic (currently 350M: China-90M; India-50M) to assail the human species, afflicting all ages and all populations across the globe. It is preceded by a state of insulin resistance, which subsequently develops into full blown type 2 diabetes. Both type 1 and type 2 diabetes ultimately involve the regular administration of insulin or its equivalent and have serious long term consequences. The syndrome is also intrinsically linked with cardiovascular disease.
This project involves an interdisciplinary approach combining computational chemistry and drug design with synthesis/medicinal chemistry and biochemistry (assay development). The project is collaborative in nature involving Dr John Stephens (Chemistry/Medicinal Chemistry, MU), Prof John Findlay (Biochemistry, MU) and Dr Gemma Kinsella (Computational Chemistry, MU). Novel structures are selected/designed employing a mix of computational chemistry and rational design. The selected compounds are synthesised and evaluated for their anti-diabetic effects. Selected compounds are optimised (chemically) to improve their biological activity and drug-like properties. Several hit compounds have been developed generating exciting biological results. A patent application and publications are in preparation.
Unique selling points of PhD project in MU:
Equipment: There is access to fully equipped and modern chemistry and biochemistry laboratories as well as computational chemistry software and hardware.
The chemistry laboratory equipment list includes NMR, MS, HPLC, GC, IR, UV, CHN microanalyser, microwave synthesizer and Schlenk lines.
The biochemistry lab has modern equipment for cell culture, protein expression/purification and radiation suites with liquid scintillation counters (e.g. a Skatron Micro 96 cell harvester and a Perkin Elmer 1450 Microbeta scintillation counter).
For the computational aspects of the project, there is substantial High Performance Computing (HPC) Facility at Maynooth University. This currently consists of an SGI Altix 8200 ICE cluster (Sioc) with 43 compute nodes. Each node has two Intel(R) Xeon(R) CPU E5440 "HarperTown" quad-core processors, which totals 344 CPU cores and 344 Gigabytes of memory in the system. Maynooth University has also contributed to the Irish Centre for High-End Computing (ICHEC's) Stokes cluster, which gives the research community at Maynooth University direct access to 168 CPU core units.
Multi-disciplinarity: This project is very interdisciplinary in nature combining computational chemistry, synthetic/medicinal chemistry and biochemistry. It offers a rare opportunity to gain valuable experience at scientific interfaces allowing students to obtain a unique skill set in chemistry and biology. The student will have the opportunity to spent time working in the biochemistry and chemistry laboratories.
Industry: The project is attracting significant industrial interest due to the novel science, intellectual property and valuable compounds being generated. Students currently working on this project have sent time on placement in industry.
Structure PhD programme: Dr Stephens participates and contributes to the structured PhD programme in the Chemistry Department at Maynooth University.
The Stephens group carries out research in synthetic organic chemistry with a focus on asymmetric synthesis and medicinal chemistry.
Dr Stephens’ interest in asymmetric synthesis lies in the efficient control of selectivity (enantio-, diastereo, regio-, and chemo-) in bond making reactions, particularly C-C bond making processes. The demand for new and economical asymmetric reactions is being driven by the pharmaceutical industry due to the chiral nature of many pharmaceutical products.
Medicinal chemistry involves the design, synthesis and development of new pharmaceutical drugs that are suitable for therapeutic use. Dr Stephens has a particular interest in diabetes, neurological disorders and microbial infections and is currently investigating new routes to novel chemical therapies.
Dr Stephens is also interested in the design, synthesis and application of novel fluorophores(fluorescent organic molecules) and investigating and elucidating biosynthetic pathways in microorganisms.