PhD Studentship in Primate Comparative Genomics: Exploring Somatic Mutations and Ageing Across Evolutionary Timescales

Are you passionate about understanding the fundamental mechanisms of evolution and aging? Join us at the University of Cambridge to investigate how genomic instability influences lifespan and aging across diverse primate species. This fully funded PhD studentship offers an exciting opportunity to work at the cutting edge of evolutionary genomics and contribute to groundbreaking research.

About the Project

How do some primates live over twice as long as others, and what can this teach us about human ageing? This PhD project offers a unique opportunity to investigate how somatic mutations, clonal dynamics, and genomic maintenance shape ageing and lifespan across diverse primate species.

Somatic mutations accumulate in healthy cells over time [1]. They underpin the development of cancer and have been hypothesised to contribute to ageing [2]. Studying them in normal tissues has only recently become feasible due to advances in the accuracy of genome sequencing [3]. Recent studies in humans have revealed that somatic mutation rates vary substantially between cell types. While across mammals the somatic mutation rate correlates inversely with species lifespan [4]. Non-human primates provide a unique opportunity to understand the principles that govern somatic evolutionary processes, due to their close phylogenetic proximity to humans and broad range of lifespans and life-histories.

Building on cutting-edge methods such as NanoSeq ultra-accurate sequencing and long-read PacBio sequencing, this research will map the somatic mutational landscapes of multiple tissues across diverse species of primates, spanning over 70 million years of evolution. The findings will provide fundamental insights into how genomic instability contributes to ageing and age-related diseases while revealing the evolutionary innovations that underpin human longevity.

Key objectives include:

1. Creating a Primate Somatic Mutational Atlas: Characterising somatic mutation rates, signatures, and structural variation across species with lifespans ranging from 5 to 80 years.
2. Investigating Clonal Dynamics: Understanding how positively selected mutations drive clonal expansions in tissues across lifespans.
3. Uncovering Genetic Determinants of Longevity: Identifying the DNA repair mechanisms and somatic maintenance pathways that distinguish long-lived species from their shorter-lived counterparts.

You will collaborate closely with world-class researchers, including groups at UC Berkeley and the Wellcome Sanger Institute, and benefit from access to state-of-the-art facilities at the University of Cambridge.

Training and Techniques Provided:

This interdisciplinary project will involve a combination of experimental and computational approaches. You will gain expertise in:

• Genomic Technologies: Laser capture microdissection, NanoSeq, and long-read sequencing.
• Computational Biology: Somatic mutation and clonal dynamics analysis using bioinformatics pipelines.
• Comparative Genomics: Cross-species analysis of mutational signatures and evolutionary traits.
• Scientific Communication: Writing publications, presenting at conferences, and engaging with public audiences.

Candidate Requirements:

We are seeking a highly motivated candidate with

• A First or Upper Second-Class UK Honours degree (or international equivalent) in Genetics, Biology, Bioinformatics, or a related field.
• Interest in evolutionary biology, ageing, and genomics.
• Experience in molecular biology or bioinformatics (desirable but not essential).
• Strong analytical and collaborative skills, with the ability to work independently in a supportive research environment.

Why Join Us?

As part of this studentship, you will:

• Be at the forefront of research in evolutionary genomics and ageing.
• Work with leading experts and innovative technologies in a supportive academic environment.
• Have the opportunity to present your work at international conferences.
• Gain valuable skills for careers in academia, industry, or policy.

Group Website: https://www.alexcagan.com/

The Department of Genetics: https://www.gen.cam.ac.uk/

Why Cambridge?

The University of Cambridge offers an inspiring environment for research, with a rich academic tradition, world-class facilities, and a supportive community. As part of the Department of Genetics, you will join a diverse and vibrant cohort of students and researchers working on some of the most pressing questions in science.

How to apply:

For more information, please contact Dr Cagan by email before applying [Email Address Removed]. Please email a CV and a cover letter explaining your motivation to pursue a PhD in this area, outline your research interests and background, and describe the qualities and experience you will bring to the role.

A formal application must be submitted by 7^th January 2025 through the Cambridge University Applicant Portal (https://www.postgraduate.study.cam.ac.uk/courses/directory/blgepdphg) for the course "PhD in Genetics" commencing October 2025, naming Dr Alex Cagan as potential supervisor. Interviews are likely to take place in January 2025. See also https://www.gen.cam.ac.uk/postgraduate/postgraduate-apply