PhD Studentship in Chemistry - Kynurenine Pathway Enzymes as Targets for the Treatment of Alzheimer’s Disease and Psychiatric Disorders @ Newcastle University

Postgraduate Opportunities

Newcastle University

Reference code: CY026
Closing date: Starting 26 September 2016 for 3 years.
Supervisors: Dr Agnieszka Bronowska, School of Chemistry
Sponsor: School of Chemistry
Duration of the award: Starting 26 September 2016 for 3 years.
Person Specification
The successful candidate will have an excellent first degree in computational chemistry, pharmaceutical chemistry, pharmacy, physical chemistry or a related subject (e.g. biophysics, bioinformatics). They will demonstrate skills in theoretical chemistry and familiarity with the pre-clinical drug development.
Previous experience with the software packages used for MD simulations, molecular docking, virtual screening, and QM calculations, is an advantage. Experience with force field development would be highly desirable. Good programming skills are desirable but not essential.
Project Description
Kynurenine pathway (KP) enzymes, in particular IDO1 and TDO2, are of significant interest as molecular targets in immuneoncology and psychiatry. Evidence exists of a link between increased IDO1 activity and depression, as well as between upregulated KP enzymes and a cognitive decline in Alzheimer’s Disease (AD). Notably, depressive symptoms affect the majority of AD's patients. Up-regulation of KP enzymes has been implicated in schizophrenia, major depressive disorder (MDD) and suicidality in adults and adolescents. Further support for a link between KP elevation, neuroinflammation, and depressed mood are found in patients with autoimmune diseases. Thus, discovery of potent and selective inhibitors of KP enzymes is very attractive for development of innovative drugs targeting chronic, devastating, and currently untreatable conditions.
This studentship seeks to identify and develop novel, potent and selective inhibitors of KP enzymes, in particular IDO1 and TDO2, which can be developed as medicines for the treatment of AD and psychiatric disorders, such as depression, bipolar disorder, and schizophrenia, by means of molecular docking, MD simulations, and QM calculations. Subsequently, the project will focus on thermodynamics of their binding to the target protein, and understanding of the role of all components driving the association, most notably protein’s configurational entropy and allosteric effects. Development of potential covalent inhibitors is also among the goals of the project. The project would provide a strong training in the fields of computational chemistry and structure-based molecular design. As such, this would provide an ideal experience for a future career in the pharmaceutical industry.

Funding information

Value:

100% tuition fees at the UK/EU rate and an annual stipend (£14,296)

Funding applies to:

Open to applicants from a range of countries

Contacts and how to apply

Academic contact:

For further details please email Dr Agnieszka K Bronowska: agnieszka.bronowska@ncl.ac.uk

Administrative contact and how to apply:

The candidate must apply through the University’s online postgraduate application form. Only mandatory fields need to be completed however, you will need to include the following information:
- insert the programme code: 8100F in the programme of study section
- select ‘PhD School of Chemistry (full time) - Chemistry ’ as the programme of study
- insert the studentship code CY026 in the studentship/partnership reference field
No personal statement is required but please attach a covering letter, CV and (if English is not your first language) a copy of your English language qualifications. The covering letter must state the title and code of the studentship, and state how your interests and experience relate to the project.

Application deadline:

1 July 2016