Functional Evaluation of Risk Genes in Early Breast Cancer

Genome-wide association studies (GWAS) have identified numerous genetic loci associated with breast cancer risk. However, translating these statistical associations into biological understanding requires direct experimental interrogation of candidate genes and regulatory elements. Our laboratory investigates how inherited genetic variation contributes to the earliest stages of breast tumorigenesis. We focus particularly on early pre-invasive lesions and the cellular transitions that precede invasive disease. Using CRISPR-based genome engineering, next-generation sequencing, proteomics, and in vivo models, we functionally evaluate candidate risk genes to define their roles in epithelial transformation, cell fate, and tumour initiation.

By integrating human genetics with experimental cancer biology, this work aims to identify mechanisms driving early disease and uncover new opportunities for prevention and interception.

Depending on level and experience, student projects may involve:

• CRISPR-based gene perturbation (knockout, activation, or repression) in breast epithelial cell models
• Functional assessment of candidate risk genes using in vivo mouse models
• Multi-omic analysis following genetic perturbation (transcriptomics, proteomics)
• Characterisation of phenotypes relevant to early tumour development (proliferation, differentiation, invasion, immune interactions)
• Validation of candidate therapeutic vulnerabilities.

Students will gain hands-on training in:

• CRISPR genome editing and molecular cloning
• Mammalian cell culture
• In vivo models of breast cancer
• Next-generation sequencing library preparation and analysis
• Experimental design and translational research strategies.

Projects are conducted within a collaborative environment that integrates genetic discovery with mechanistic experimentation. Students will work closely with computational biologists to
prioritise candidate genes and with cancer biologists to evaluate functional outcomes.

This project would suit students with a background in genetics, molecular and cell biology with a strong interest in cancer biology and translational research.