125th Anniversary PhD Scholarship in Cancer and Genomic Sciences - PhD Project: Identifying novel therapies to alleviate the neurotoxic side-effects of chemotherapy.

About the project

Neurotoxicity is a major side-effect of chemotherapy drugs 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. Symptoms occur acutely during treatment but can also build up over months and persist for months or years after the end of treatment with major impact on the quality-of-life for cancer survivors. There are currently no effective treatments to reduce either the peripheral neuropathy or cognitive effects.

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. We have shown that targeting the DNA damage response is neuroprotective in pre-clinical models of multiple different forms of neurological disease, including both acute and chronic disease. These neurological disorders all feature unrepaired DNA damage in neurons, which is also a feature of chemotherapy-induced neurotoxicity. Hence, it is possible that the same approach will prove to be neuroprotective and ameliorate the side-effects of chemotherapy.

In the first part of the project, the student will examine activity changes occurring in the brain following chemotherapy treatment. The student will culture neurons and organotypic slices from the cortexes of mice on multi-electrode arrays to examine the effect of chemotherapy drugs in both 2D and 3D brain networks. We will then try to 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 can see that treatment with cisplatin results in a memory deficit reminiscent of the commonly reported cognitive effects in patients. Cisplatin also causes hypersensitivity to temperature, which mirrors one aspect of the peripheral neurotoxicity in patients. The student will use optogenetics to acutely inhibit or activate specific classes of neuron in the learning centres of the Drosophila brain and in the nociceptive sensory neurons in the peripheral nervous system. These techniques, coupled with the precision genetics of Drosophila will allow the student to knockdown expression of key DNA damage response components and candidate downstream effectors to identify which pathways downstream of DNA damage are mediating the neurotoxicity.

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

Find out more and apply

Who can apply?

These scholarships are designed to create opportunities and address the underrepresentation of talented Black or Black mixed heritage students in academia. Applicants who meet all of the following criteria are eligible to apply:

1. Students classified as 'Home' for tuition fee payments
2. Members of one of the following ethnic groups:

• Black African
• Black Caribbean
• Black Other
• Mixed – White and Black Caribbean
• Mixed – White and Black African
• Other mixed background (to include Black African, Black Caribbean or Black Other)

      3. Not already enrolled on a PhD programme at the University of Birmingham

What does the scholarship provide?

1. Financial Support: Recipients of these scholarships will receive substantial financial support, including a stipend at UKRI rates, which is set at £20,780 per year for the 2025/26 academic year, and will be paid to you in regular instalments. Successful awardees will also have their tuition fees covered at a minimum of £5,006 per year. This support is designed to alleviate the financial burden often associated with pursuing a doctoral degree, such as covering tuition fees, living expenses, and research-related costs.
2. Mentorship and Guidance: Scholarship recipients will benefit from mentorship opportunities and guidance from accomplished faculty members who are dedicated to helping them succeed in their academic and research endeavours.
3. Research Opportunities: We are committed to providing an exceptional research environment. Students will have access to state-of-the-art facilities, cutting-edge resources, and a vibrant scholarly community.
4. Community Building: A key component of the scholarship programme is the creation of a supportive community of Black British researchers pursuing PhDs. This network will foster collaboration and peer support among scholars.
5. Research Training Support Grant: In addition to financial support, scholarship recipients will receive a research training support grant at £2,250 across the duration of the PhD. This grant is intended to support conference attendance, fieldwork, and other essential activities that enhance their research and academic growth.
6. Commitment to Inclusivity: We are dedicated to building an inclusive academic environment that values diversity and ensures equitable access to education.