125th Anniversary Scholarship for Black British Researchers - Identifying Novel Therapies to Alleviate The Neurotoxic Side-effects of Chemotherapy

Neurotoxicity is a major side-effect of chemotherapy drugs that are used to treat many common cancers, including bowel, breast and lung cancers. Patients commonly suffer from peripheral nerve pain, loss of feeling and sensation in the fingers and toes, hypersensitivity to both cold and heat. Patients also report cognitive effects, including loss of concentration and memory. Symptoms are often so extreme that drug doses have to be reduced or treatment curtailed. There are currently no effective treatments to reduce either the peripheral neuropathy or cognitive effects, which are caused by damage to DNA.

In this project, the student will take a multi-system approach to test a novel therapeutic strategy with the potential to ameliorate both peripheral and central symptoms. In the first part of the project, the student will examine activity changes occurring in the brain following chemotherapy treatment. The student will use cultured neurons and organotypic brain slices to examine the effect of chemotherapy drugs in both 2D and 3D brain networks via multi-electrode arrays. We will then block these changes using brain-penetrant inhibitors of the DNA damage response.

The second part of project will study the peripheral and cognitive effects of chemotherapy drugs on fruit flies by harnessing the power of Drosophila genetic screens to identify novel pathways acting downstream of the drugs. We have developed a robust short-term memory assay in Drosophila and have observed that cisplatin results in a memory deficit reminiscent of the commonly reported cognitive effects in patients and also causes hypersensitivity to temperature, which mirrors one aspect of peripheral neurotoxicity in patients. The student will use optogenetics to acutely inhibit or activate specific classes of neurons, coupled with the precision genetics of Drosophila which will allow the student to inhibit key DNA damage response components and candidate downstream effectors to identify which pathways downstream of DNA damage are mediating the neurotoxicity.

Finally, the student will use a combination of existing transcriptomics data and targeted Western blot to analyse key changes in cultured neurons exposed to chemotherapy drugs and co-administered with inhibitors of the DNA damage response. Together with the first two parts of this project, this approach will help us understand the neuroprotective effect of the DNA damage response inhibitors and potentially identify new drug targets for neuroprotection.

Your supervisory team

The lead supervisor for the PhD project is Dr Richard Tuxworth, an Associate Professor and the Deputy Head of Education in Cancer and Genomic Sciences, who is a neurobiologist with a particular interest in understanding DNA damage in neurological disease. The co-supervisors are Professor Zubair Ahmed, a Professor of Neuroscience with an extensive background in the mechanisms of neurotoxicity and Dr Felix Chan, an Assistant Professor in Pharmacology, who is a neuroscientist by training, but has a wide-ranging interest in studying metabolism and mitochondrial function in the body.

For more information and to apply on-line, please click the above “Apply” button.

Funding Details

Additional Funding Information

The University of Birmingham is proud to celebrate its remarkable 125-year journey and announce the launch of a groundbreaking scholarship initiative designed to empower and support Black British researchers in their pursuit of doctoral education.

These newly established 3.5-year scholarships aim to address underrepresentation and create opportunities for talented individuals from diverse backgrounds to excel in academia. You can find out more here: https://www.birmingham.ac.uk/study/postgraduate/research/funding/black-british-researchers-scholarship

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