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Molecular characterisation of a novel transporter for the atypical antipsychotic clozapine


   Institute of Systems, Molecular and Integrative Biology

  , Prof M Pirmohamed  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Applications will be reviewed until a suitable candidate is appointed.

Schizophrenia is a severe psychiatric illness affecting about 24 million people worldwide. Schizophrenia can have a devastating effect on a patient’s life and is associated with increased mortality, with life expectancy reduced on average by 15 years compared to that of the general population. Pharmacological treatment is of fundamental importance for coping with the symptoms of schizophrenia. However, about one-third of all patients do not respond adequately to standard treatment options and remain refractory. A patient is classified as refractory if treatment with at least two antipsychotic drugs, has failed. Clozapine is approved for the treatment of schizophrenia in otherwise refractory patients and has demonstrated clear superiority to typical antipsychotics. Despite being effective, clozapine is only licensed as a treatment option for refractory patients because of the substantially increased risk of agranulocytosis (loss of neutrophils).

We have previously shown that clozapine is transported by an unidentified membrane transporter that could be important in the response to the drug and/or side effects. Using cutting edge molecular biology methodology, we have recently identified a specific transporter for clozapine. The successful student will explore and characterises this membrane transporter, in particular how this relates to efficacy and toxicity profile of clozapine. This is an exciting project that will provide the student with training and expertise in pharmacological techniques, cell biology and pharmacogenetics.

The project is suited to a candidate with a degree related to biological or life sciences with an interest in pharmacology, drug safety and/or schizophrenia. Please contact Dr David Dickens () for additional information and to enquire on the application process.


Funding Notes

The project is open to both UK, European and International students. It is UNFUNDED and applicants are encouraged to contact the Principal Supervisor directly to discuss their application and the project. Assistance will be given to those who are applying to international funding schemes.
The successful applicant will be expected to provide the funding for tuition fees and living expenses as well as research costs. There is NO funding attached to this project
Details of costs can be found on the University website:
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A £2000 ISMIB Travel and Training Support Grant may be available to new self-funded applicants.

References

Dickens D, Rädisch S, Chiduza GN, Giannoudis A, Cross MJ, Malik H, Schaeffeler E, Sison-Young RL, Wilkinson EL, Goldring CE, Schwab M, Pirmohamed M, Nies AT. Cellular Uptake of the Atypical Antipsychotic Clozapine Is a Carrier-Mediated Process. Mol Pharmaceut. 2018. 15, 3557-3572. DOI: 10.1021/acs.molpharmaceut.8b00547

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