Job Description

Ref Number

B02-09637

Professional Expertise

Research and Research Support

Department

School of Life & Medical Sciences (B02)

Location

London

Working Pattern

Full time

Salary

43,981-52,586

Contract Type

Permanent

Working Type

On site

Available for Secondment

No

Closing Date

31-Oct-2025

About us

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UCL is one of the UK's premier research and teaching Universities (www.ucl.ac.uk) and has one of the largest Biomedical Faculties in Europe. UCL is both a Cancer Research UK Centre and an Experimental Cancer Medicine Centre providing key infrastructure for cancer research. The UCL Cancer Institute is a 40 million investment in central London based at University College London (UCL), one of the world's top universities and a founding member of the Crick Institute. UCL Cancer Institute draws together over 300 scientists working together to develop world-class basic and translational cancer research. Through our associations with UCL Hospitals NHS Foundation Trust, Great Ormond Street Hospital and the Royal Free Hospital NHS Foundation Trust, the Institute has greater clinical links than any comparable centre in the UK and a significant impact on the delivery of clinical service to cancer patients. This concentration of excellence, access to patients and significant recent investment of cancer treatment and research infrastructure makes UCL a global leader.

About the role

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Mismatch repair-deficient (MMRd) cancers represent a biologically distinct subgroup of malignancies characterised by a high mutational burden resulting from defects in the DNA mismatch repair system. These defects lead to widespread microsatellite instability (MSI), genomic hypermutation, and a high frequency of frameshift mutations, which in turn generate a large repertoire of neoantigens. This antigenic load makes MMRd tumours particularly immunogenic, setting the stage for robust immune recognition and making them compelling candidates for immunotherapy.



Immune checkpoint inhibitors (ICIs), particularly those targeting PD-1/PD-L1 pathways, have shown unprecedented efficacy in treating MMRd tumours across multiple cancer types, including colorectal, endometrial, and gastric cancers. The success of ICIs in this context led to the first tumour-agnostic FDA approval for pembrolizumab in MMRd or MSI-high solid tumours. However, despite these advances, a significant proportion of patients with MMRd cancers fail to respond or eventually develop resistance to immunotherapy. This has prompted an urgent need to understand the mechanisms underlying primary and acquired resistance within this immunogenic yet clinically heterogeneous group.



Emerging evidence suggests that MMRd cancers evolve under intense immune selection pressure, resulting in complex evolutionary dynamics. Immune escape mechanisms -- including loss of antigen presentation machinery, mutations in interferon signalling pathways, and clonal diversification -- may drive tumour progression and therapeutic resistance. Tumour evolution in this context is not linear but involves branching trajectories influenced by both intrinsic genomic alterations and extrinsic immune factors. Studying these processes requires high-resolution longitudinal and spatial profiling of the tumour and microenvironment, particularly before, during, and after immunotherapy.



Recent studies have begun to unravel how immunoediting shapes clonal architecture in MMRd tumours, with some resistant clones emerging from pre-existing subpopulations and others evolving de novo under treatment pressure. These dynamics can be highly patient-specific, suggesting that a personalised understanding of tumour evolution and immune evasion is critical. Integrating genomic, transcriptomic, and spatial data offers a powerful approach to reconstruct these evolutionary pathways and identify predictive biomarkers of response or resistance.



In this context, the continued study of MMRd cancer evolution, particularly using cutting-edge computational methods and large, clinically annotated datasets, remains a high priority. Future work will benefit from the integration of single-cell and spatial technologies to map tumour-immune interactions in situ, and from novel computational frameworks capable of capturing complex clonal behaviours. Insights from such studies have the potential to inform rational combination therapies, guide patient stratification, and ultimately improve outcomes for individuals with MMRd cancers undergoing immunotherapy.

The role will be available for 3 months in the first instance

Appointment at Grade 7 is dependent upon having been awarded a PhD

; if this is not the case, initial appointment will be at Research Assistant Grade 6B, with payment at Grade 7 being backdated to the date of final submission of the PhD thesis.

Applications should include a CV and a Cover Letter:

In the Cover Letter please evidence the essential and desirable criteria in the Person Specification part of the . (By including a Cover Letter, you can leave blank the 'Why you have applied for this role' field in the application form, which is limited in the number of characters it will allow.)

About you

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Successful candidates must have a Postdoctoral qualification (PhD), and experience in presenting complex scientific concepts and content both in writing and verbally. They will show a strong commitment to the lab mission and embody its values through excellent collaborative interpersonal skills with an ability to work cooperatively in a multidisciplinary setting.



Further, excellent communication skills and the ability to work well in a multidisciplinary team and to train juniors are essential. The post-holder will be expected to have the ability to assist other members of the lab, supervise MSc students, collaborate with external research groups, as well as contributing to the organisation and smooth operation of the lab.

What we offer

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As well as the exciting opportunities this role presents we also offer some great benefits some of which are below:


41 Days holiday (including 27 days annual leave 8 bank holiday and 6 closure days) Defined benefit career average revalued earnings pension scheme (CARE) Cycle to work scheme and season ticket loan On-Site nursery On-site gym Enhanced maternity, paternity and adoption pay Employee assistance programme: Staff Support Service Discounted medical insurance

Please visit https://www.ucl.ac.uk/work-at-ucl/rewards-and-benefits to find out more.

Our commitment to Equality, Diversity and Inclusion

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As London's Global University, we know diversity fosters creativity and innovation, and we want our community to represent the diversity of the world's talent. We are committed to equality of opportunity, to being fair and inclusive, and to being a place where we all belong.



We therefore particularly encourage applications from candidates who are likely to be underrepresented in UCL's workforce.



These include people from Black, Asian and ethnic minority backgrounds; disabled people; LGBTQI+ people; and for our Grade 9 and 10 roles, women.



You can read more about our commitment to Equality, Diversity and Inclusion here : https://www.ucl.ac.uk/equality-diversity-inclusion/