LifeArc Rare Disease PhD Doctoral Training Programme – Targeting the DNA damage pathway as a therapy for amyotrophic lateral sclerosis

A fully funded 4-year PhD position (UK students only) is available from October 2025 in the labs of Professor Zubair Ahmed (https://www.birmingham.ac.uk/staff/profiles/inflammation-ageing/ahmed-zubair) and Dr Richard Tuxworth to study DNA damage signalling in neurodegenerative disorders. The project will target the DNA damage signalling pathway using small molecule inhibitors and adeno-associated virus (AAV)-based gene therapy to promote neuroprotection, slow disease progression and promote recovery of lost function in preclinical models of ALS. We will block components of the DNA damage pathway using Drosophila models of ALS and assess neuronal function using movement assays, synapse retraction, and monitor cell death and DNA damage signalling molecules. We will also use human iPSC motor neurons from ALS patients and assess DNA damage after exposure to genotoxic agents. We will then block components of the DNA damage pathway using small molecule inhibitors and neuron-specific AAV-based gene therapy to promote neuroprotection. Finally, we will test our optimised neuron specific AAV-based gene therapy treatment in preclinical models of ALS and assess neuroprotection and slowing of disease progression using established molecular and behavioural tests.

This project is part of the LifeArc Rare Disease PhD Doctoral Training Programme and is expected to develop small molecule and gene therapy-based approaches for the treatment of ALS and other rare neurodegenerative disorders.

LifeArc Rare Disease PhD Doctoral Training Programme: Globally, there are more than 300 million people living with rare diseases. However, clinical trials for rare diseases are challenging and can be a major limiting step in getting new treatments to patients. The research can be fragmented, and researchers sometimes lack access to specialist facilities, as well as advice on regulation, trial designs, preclinical regulatory requirements, and translational project management.

The LifeArc Centre for Acceleration of Rare Disease Trials brings together a consortium of three universities from across the UK: Newcastle University, Queen’s University Belfast, and University of Birmingham. They are pooling their expertise in a £12M Centre to focus on improving the efficiency of rare disease trials and increasing the number of opportunities for patients to take part. Researchers will develop a UK ‘4 nations’ approach to deliver trials of new treatments using ‘one stop’, patient friendly models. This will speed up the delivery of clinical trials for people with rare diseases and enable more rapid approval of new therapies for use in the NHS.

More information on the Centre can be found here: https://www.birmingham.ac.uk/research/centres-institutes/rare-disease-studies/lifearc-centre and here: https://www.lifearc.org/project/lifearc-translational-centres-for-rare-diseases/.

As part of the Centre, LifeArc and the University of Birmingham are funding 5 non-clinical PhD studentships to work on translational projects involving different rare diseases. These PhD projects will provide essential evidence and models to allow treatments to be tested in rare disease clinical trials of the future.

How to apply

Please apply directly to Professor Zubair Ahmed ([email protected]) by providing the following:

• Detailed CV, including your nationality and country of birth. 

• Covering letter (no more than 2 pages) highlighting your research experience/capabilities and why you wish to undertake a PhD in the ADRT.

• Names and addresses of two referees. 

• Copies of degree certificates with transcripts written in English. 

Deadline for applications: 22nd April 2025.