A Research Assistant position is available in the group of Prof. Gabriel Balmus at the UK Dementia Research Institute (UKDRI), Department of Clinical Neurosciences, University of Cambridge. The project investigates the function-resolved biology of ATM, a master regulator of the DNA damage response (DDR), with the goal of identifying therapeutic strategies for ataxia telangiectasia (A-T) and ATM-deficient cancers. The post-holder will map how ATM protein presence and kinase activity differentially regulate DDR signalling, repair pathway choice, and cell fate across distinct genotoxic contexts.
ATM coordinates responses to DNA double-strand breaks (DSBs), replication stress, and oxidative damage, directing chromatin remodelling, checkpoint activation, and repair pathway selection. Germline loss of ATM cause A-T, a rare progressive cerebellar ataxia, while somatic ATM mutations are among the most frequent DDR alterations in human cancer. We are aware of important gaps in our understanding of ATM biology that the field has yet to fully address, and the project aims to bridge these by generating a global functional map of ATM requirement across damage contexts, integrating inducible protein degradation, genome-wide CRISPR screening, and live-cell phenotypic reporters.
A central component of the project is the identification of therapeutic candidates for A-T. The post-holder will conduct medium- to high-throughput screens of siRNAs, antisense oligonucleotides (ASOs), CRISPR gRNAs, and small molecules to identify agents that restore cellular fitness or exploit ATM-deficient states. Validated hits will be characterised mechanistically to support therapeutic target prioritisation, integrating functional genomics with translational screening in disease-relevant cellular models.
Candidates must hold a BSc in Biochemistry, Cell Biology, Molecular Biology, Genetics, or a related discipline (PhD not required). A strong practical background in cell and molecular biology is essential, including PCR/qPCR, Western blotting, DNA/RNA/protein extraction, and basic cloning, together with proficiency in mammalian tissue culture. Experience with CRISPR-based workflows gRNA design, lentiviral transduction, and functional screening - is required. Hands-on experience of human iPSC culture under feeder-free conditions is highly desirable, as iPSC-derived models will be central to the project.
Experience with DDR assays - H2AX/53BP1 immunofluorescence, comet assays, or flow cytometry-based cell cycle analysis - would be advantageous. Familiarity with interpreting output bioinformatic analyses of CRISPR screen data (e.g. MAGeCK, BAGEL2) or transcriptomic datasets is desirable but not essential, as training will be provided. Experience with ASO or siRNA delivery and knockdown validation would also be of value.
The role requires excellent organisation skills, rigorous record-keeping, and the ability to work both independently and collaboratively. The post-holder will manage their experimental programme, contribute to laboratory operations and compliance, and generate data suitable for publication and progress reporting. Close interaction with Balmus Lab members and collaborators across the UKDRI and wider Cambridge community is expected.
The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.
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