Janet Thornton Fellowship

Wellcome Sanger Institute

Applications now open for the Janet Thornton Postdoctoral Fellowship 2022

At the Wellcome Sanger Institute, we are committed to enabling and opening routes back into science for those who have had a break from scientific research - for any reason.

Read more below

Sanger Institute, Genome Research Limited

We understand that even a short time out of research can have an impact on your career, which is why we have created a postdoctoral fellowship providing an additional opportunity specifically for those who have been out of scientific research for 12 months or more to return to high-quality postdoctoral training. One Fellowship will be awarded each year. Each Fellowship will last for three years and can be worked full time, part time or flexibly.

Fellowships will be awarded after a competitive selection process, with applicants applying to one of the broad project outlines listed below. Applicants are encouraged to make contact with the named supervisor.

While the Sanger Institute provides the opportunity in its recruitment processes for job applicants to declare career breaks (taken for any reason) so that they can be taken into account when assessing applications for all roles, particularly in relation to the potential impact of time out on individuals’ scientific and career outputs, this fellowship will be open exclusively to those who have taken a career break of 12 months or more.

If you would like to learn more about a day in a life of a Janet Thornton Fellow click here

Eligibility Criteria

The Janet Thornton Fellowship is open to scientists who:

  • A minimum of 12 months break from scientific research, for any reason*
  • have at least one years’ postdoctoral research experience
  • will be able to start within 6 months of being offered the role
  • Not currently working in a scientific research role

*Our Janet Thornton Postdoctoral Fellowship is aimed at those that have taken career breaks for any reason (for example, caring for dependants, ill health or if your career has been negatively impacted by COVID-19).

Application process

The Fellowship is awarded after a competitive selection process, with applicants applying to one of the projects below. You are encouraged to make contact with the named supervisor.

You are asked to provide:
– a current CV
– the names of two referees
– Application Form

For more information on applying and guidance, please download our Application Form Guidance PDF document.

To apply please click here

Deadline

Applications now open for 2022 

Q and A – 20th June – We will be hosting a Q and A – an opportunity for you to find out more about the Fellowship, recruitment process, chat to current Postdoctoral Fellows. Please contact us for the Zoom link.

Friday 15 July 2022 – Application deadline

July – September 2022 – Shortlisted candidates will be invited to work with Wellcome Sanger Institute research lead to co-develop and bespoke the project proposal

November 2022 – Interviews
The shortlisted candidates will be invited for an interview with Wellcome Sanger Institute staff. Candidates will be asked to give a presentation and answer questions on their previous research and the developed project proposal (via Zoom). This will be followed by a Q&A-style competency-based interview with the panel.

All candidates, including those unsuccessful at this stage, will receive feedback and will have the opportunity to receive mentorship and support from members Faculty.

January 2023 – Start of the Fellowship

Details of the Fellowship

This Postdoctoral Fellowship is for a duration of three years, can be worked full time, part time or flexibly at the Sanger Institute on the Wellcome Genome Campus in Hinxton near Cambridge and includes:

  • Full Time Equivalent Salary currently – £33,272-£41,709
  • Research expenses, including generous consumables and travel costs for conferences and training courses
  • Access to training and support resources from across the organisation
  • Access to the University of Cambridge Careers Service
  • Generous and flexible benefits

Contact

For further information, please contact: Dr Saher Ahmed: saher.ahmed@sanger.ac.uk

2022 Projects

Adams Project 1 - New treatments for liver disease - experimental Cancer Genetics, Cancer Aging and Somatic Mutation Programme 

Supervisor: Dr David Adams david.adams@sanger.ac.uk

Project Outline:

More than 30 per cent of the UK adult population have a fatty liver, characterised by bland fat accumulation, while around 6 per cent have liver fibrosis, which is thought of as a precursor to liver cirrhosis, which is a progressive disease that can ultimately result in liver failure and/or liver cancer. Over the next decade the rates of liver disease are expected to skyrocket. Despite these statistics the only approaches shown to reduce the risk of disease progression are lifestyle interventions including changes in diet and exercise but few people are able to sustain these interventions long-term. Importantly, individuals at high risk of disease progression include diabetics and people of lower socioeconomic status, with there being a particularly pressing need to identify treatments for patients in these at-risk groups.

Over the last decade the Sanger Mouse Genetics Programme (MGP) has generated over 1500 mouse knockout lines. During the process of phenotyping of these lines, cohorts of animals from each knockout background were phenotyped to collect information such as liver ALT/AST/GGT values, platelet count, and blood lipid biochemistry, all of which report on liver health. In addition to this, at 16 weeks of age two male and two female animals from each line underwent a full necropsy such that tissues including the liver were collected into FFPE (histology) blocks.

As mentioned above the prevalence of liver disease is increasing dramatically and as such the pharmaceutical industry has placed an enormous amount of focus (many billions of dollars) on NAFLD/NASH and more specifically on the amelioration/reversal of liver steatosis (fat accumulation) and fibrosis. At present the best in class drugs can modestly reverse the disease in up to 30 per cent of patient, with the latest clinical trials involving drug combinations showing marginal addition benefit. Thus, there is a pressing need to identify new therapeutic targets as the intention to treat population increases.

From the abovementioned MGP, we have identified just under 1000 homozygous knockout mouse strains (932 genes) that were extensively phenotyped, and from whom liver tissue is available for analysis. The vast majority of these lines are knockouts of protein coding genes, with miRNA knockouts also represented. The genes in this collect were randomly selected and cover a vast biological space. Importantly, the mice in the MGP pipeline were fed a high-fat “Western” diet such that by 16 weeks mice showed significant liver steatosis and some showed fibrosis. Since each of these knockout lines are homozygous viable and genetically identical, with the exception that each line is null for a single gene, they represent an incredible resource in which to identify potential therapeutic targets. This project will use a range of approaches including machine learning and statistical modelling.

Adams Project 2 - The Genomic Atlas of Dermatological Tumours (DERMATLAS)

Supervisor: Dr David Adams david.adams@sanger.ac.uk

Project Outline:

Virtually no other tumour type is associated with so many different forms as skin cancer. Histologically, tumours of the skin may arise from epithelium, including epidermis, hair follicle, sebaceous or sweat gland, melanocytes, dermal-associated mesenchymal structures or tissue resident immune cells, making for a diversity of clinical presentations. Importantly, many skin tumour types have an extremely poor prognosis.

There are currently several major barriers to progress in the field of molecular skin cancer pathology. Firstly, many skin tumour subtypes have never undergone molecular profiling, or if they have, targeted sequencing has been used and the number of cases analyzed has been so limited that deriving firm conclusions about the profile of driver genes, DNA mutational signatures and germline alleles has not been possible. Virtually no studies have explored these tumours’ epigenome. Secondly, since many skin tumours are rare, no one pathologist has sufficient cases to draw statistically robust conclusions meaning that a team science approach is required if we are to comprehensively elucidate the molecular profile of these conditions. Finally, until now, the technology to analyze cases from FFPE material has been a major hurdle to progress. Thus, the experiments we are performing have recently become feasible because of technical advances in the field and the consortium of world-leading dermatopathologists we have assembled for this project.

Our overarching hypotheses for the studies proposed in this grant are that:

  1. Most skin tumour subtypes can be defined by a discrete set of drivers, some of which can be targeted therapeutically;
  2. Some skin tumours are caused by germline predisposing alleles, chemical exposures or viruses and these can be revealed by DNA/RNA sequencing and analysis, which can help define new screening and public health approaches.

We will address each of these hypotheses with the following specific objectives/aims:

  1. For 70 key skin tumour subtypes defined by the World Health Organization, that have not undergone extensive whole genome or whole exome sequencing previously, we will analyse up to 50 cases (exome and transcriptome) from a range of body sites to build a genomic atlas of dermatological tumours, including detailed maps of SNVs, copy number alterations, genome-wide methylation and expression profiles.
  2. With these sequence data we will use state-of-the-art analytical tools to identify driver genes, mutational signatures and hence exposures or endogenous processes that might promote disease development. We will also look for evidence of other factors such as viruses not previously identified in these neoplasms.
  3. Using germline data from each case we will define the possible contribution of germline alleles to tumour development, thus facilitating clinical genetics and diagnostic services.

This project would suit an applicant with skills in bioinformatics and an interest in cancer genomics, pathology or image processing.

Anderson Project - Using next-generation sequencing and high-throughput cellular phenotyping and models to understand the biological basis of inflammatory bowel disease

Supervisor: Dr Carl Anderson carl.anderson@sanger.ac.uk

Our group has a long-standing interest in the genetics of inflammatory bowel disease (IBD). IBD is a chronic, debilitating disorder of the gastrointestinal tract that affects around 0.5% of the population, with a typical onset in early adulthood. Many IBD patients ultimately require major abdominal surgery, resulting in lifelong disability, because an appropriate drug either does not exist or is not administered soon enough. Total healthcare costs in the UK are estimated to be over £1 billion per year (Cummings et al., 2008). Disease pathogenesis is poorly understood but is likely driven by a dysregulated immune response to commensal gut microorganisms in genetically susceptible individuals. IBD is highly heritable and the group has played a leading role in the identification of over 240 regions of the genome associated with disease susceptibility. These loci were predominantly detected via genome-wide association studies and are driven by common genetic variants.

Together with our collaborators, we are generating a number of large-scale genetic and genomic datasets and resources to better understand the biological basis of IBD susceptibility, disease progression and drug response. These include:

  1. Whole-exome sequencing data for almost 100,000 IBD patients and 500,000 population controls.
  2. Single-cell RNA sequencing data from gut biopsies and blood samples from thousands of individuals, both with and without IBD.
  3. Genome-wide CRISPR screens in primary immune-cells ascertained from individuals with and without IBD.
  4. Mucosal organoids for hundreds of genotyped IBD patients.

We’re keen to receive applications from individuals who have a vision for using one or more of these datasets to help us deliver on our mission of building new therapeutic hypotheses and expediting personalized medicine for IBD. We’re also excited to hear candidate-driven project proposals that utilize the Sanger Institute’s large-scale data generation platforms, and/or our established national network of gastroenterologists for sample ascertainment and clinical input, to build novel datasets that can be applied to deliver on these goals. The team currently consists of computational geneticists, cell biologists, computer scientists, immunologists and clinicians, and we are keen to hear from applicants across this broad range of backgrounds.

Jones Project - How mutants take over aging tissues

Supervisor: Dr Phil Jones phil.jones@sanger.ac.uk

We are group of experimental and computational researchers interested in the very earliest stages of cancer development. The group culture is to work as a team in multidisciplinary projects.   We are keen to receive applications from individuals wanting to apply cell and molecular biology lab skills and develop their knowledge of screening approaches to a solving a central challenge in the field, which may lead to new methods to prevent cancer.

Background

Somatic mutations accumulate in our stem cells throughout life, but a few alter cell behaviour to generate clones that outcompete their neighbours and spread through the tissue, so that by old age we become a patchwork of mutant clones (PMC7116717, PMC6298579).  Some of these mutants are linked to diseases such as cancer, some may even be beneficial and prevent cancer.  If we can understand the mechanisms mutants use to colonise tissues, it may be possible to remove undesirable mutants from normal tissues and prevent disease.

The project

This project will exploit our new 3D primary cell culture system that recapitulates mutant clone competition and enables large scale CRISPR Cas9 gene screens, not previously been possible in primary cells, in multiple epithelial tissue types.

Project aims are:

  1. Phenotyping mutant clones: Pools of mutant genes known to colonize aging human epithelia tissues will be phenotyped with single cell RNA sequencing (Perturb-seq) in a range of tissues. This will define the cell states of expanding mutant clones for each gene.
  2. Genetic determinants of mutant fitness: Representative mutant genes with a similar phenotype will undergo a CRISPR deletion screen to define the genes they use to gain a fitness advantage.
  3. Environment and Fitness: The effects of environmental stresses on the competitive fitness of selected mutants will be determined.  Environmental factors selected will be guided by the genetic dependencies of each mutant.

Along with the experimental methods, the project will also offer training and experience in data analysis and visualization from experienced researchers in informatics and statistics.

Teichmann Project - Genomic and computational dissection of tissue architectures

Supervisor: Dr Sarah Techimann sarah.teichmann@sanger.ac.uk

Single cell genomics and spatial gene expression technologies can now be combined to provide high resolution maps of tissues. These methods are now routine, robust and scalable, and can be applied to mapping tissues in human development as well as mature adult tissues across the lifespan and across genders, and in health versus disease states. There are fundamental questions about cell lineages (e.g.in haematopoiesis, immunity, etc.), systems (e.g. skin, vasculature, immunity) and organs (e.g. kidney, lung, reproductive tissues, endometrium/decidua etc.) that can be addressed with these approaches.

We welcome postdoctoral projects that focus on specific biological tissues or systems, as well as on general overarching questions that span multiple tissues. We also value methods development projects (computational or experimental) that advance the study of tissue architectures using genomics technologies.

Vento-Tormo/Kelava Project - Establishment of endometriosis lesion-organoid screening platform

Supervisors: Dr Roser Vento-Tormo roser.vento@sanger.ac.uk and Dr Iva Kelava iva.kelava@sanger.ac.uk

Project outline:

Endometriosis is a common condition characterised by the growth of endometrial tissue outside the uterus (called “lesions”). It affects at least 10 per cent of women of reproductive age and is accompanied by many symptoms, including pain and issues with conception. Despite the high prevalence of the disease, non-invasive diagnostic tests and efficient, well-tolerated treatments are almost completely lacking. Current treatments are limited to surgical and/or hormone/analgesic treatment, both being associated with high morbidity and significant side-effects. Therefore, there is an urgent unmet clinical need for reliable non-invasive diagnostic tools and novel therapeutic approaches. Also, there is a lack of knowledge of the cellular origins and composition of endometrial lesions. The project is aimed to address those knowledge gaps by using single-cell multiomics data produced by our team to generate a model of endometriosis lesions derived from patients. To do so, we want to adapt current protocols to derive organoids from endometriosis lesions (see recent publication by our team in Nature Genetics) and establish co-culture conditions for a robust multilineage organoid platform. The development and validation of this system will be invaluable for identifying new therapeutic targets and performing drug-screenings.

In our work we combine state-of-the art genomics technologies – single cell transcriptomics, multiomics and spatial transcriptomics to determine molecular pathways involved in development and disease, with a strong focus on gynaecological disorders. We welcome applicants with interest in organoids and complex co-culture methods, but also those with computational methods development background. The current team is comprised of experts in computational methods, organoid techniques, histology and tissue processing. We are also fostering strong connections with endometriosis clinics as part of our worldwide multicentre biobank.