Janet Thornton Projects 2023_24

Janet Thornton Fellowship Projects 2023

Janet Thornton Fellowship The Janet Thornton Fellowship, designed to support scientists who have taken a career break, was named in honour of Professor Dame Janet Thornton, former Director of the EMBL- European Bioinformatics Institute (EMBL-EBI). The postdoctoral fellowship is aimed at getting scientists back into scientific research if they have had a career break of a minimum of 12 months. The fellowship was launched in 2014, as part of the Sanger Institute’s commitment to retaining and developing talent. Professor Dame Thornton has experienced first-hand the challenges of taking a career break and working flexibly in demanding scientific roles and raising a family. Eligibility Criteria Stage 1 of the Application process: The Janet Thornton Fellowship is open to Please apply to the Janet Thornton Fellowship scientists who: vacancy via our job site • A minimum of 12 months break from Please have a copy of your current CV ready to upload scientific research, for any reason* Stage 2 of the Application process: • have at least one years’ postdoctoral research If you meet the eligibility criteria we will invite you to complete stage 2 of the application experience process. Application form with a number of • will be able to start within 6 months of being questions (between 1000 – 1500 words across the questions): offered the role • Why are you interested in applying to this • Not currently working in a scientific research project outline? role • How do you think your research experience Our Janet Thornton Postdoctoral Fellowship is aimed at those that have taken career breaks for and broader contributions to the research any reason (for example, caring for dependants, environment will enrich your Fellowship ill health or if your career has been negatively experience at the Sanger Institute impacted by COVID-19). • What academic achievements are you most Application Process proud of? The Fellowship is awarded after a competitive • What personal achievements are you most selection process, with applicants applying to proud of? one of the projects below. You are encouraged to make contact with the named supervisor.

Projects for 2023 Single cell genomics and spatial gene expression technologies can now be combined to provide Unveiling Somatic Mutation Landscapes high resolution maps of tissues. These methods in Ageing Normal Cells: Implications for are now routine, robust and scalable, and can be Health and Disease applied to mapping tissues in human Supervisor: Raheleh Rahbari development as well as mature adult tissues Contact: [email protected] across the lifespan and across genders, and in We are conducting innovative research on health versus disease states. There are somatic evolution and their implications in fundamental questions about cell lineages (e.g.in cancer transformation, developmental disorders, haematopoiesis, immunity, etc.), systems (e.g. and ageing. Despite the vital role of somatic skin, vasculature, immunity) and organs (e.g. mutations, our understanding of their prevalence kidney, lung, reproductive tissues, endometrium/ and impact on normal tissues has been limited decidua etc.) that can be addressed with these by the constraints of conventional sequencing approaches. techniques. Our group has a longstanding We welcome postdoctoral projects that focus on interest in studying genetic changes in both specific biological tissues or systems, as well as normal and precancerous tissues, with a specific on general overarching questions that span focus on elucidating how ageing and other multiple tissues. We also value methods factors may contribute to cancer development development projects (computational or and potential disease predisposition in future experimental) that advance the study of tissue generations. architectures using genomics technologies. To achieve these goals, our team utilises state-of- the-art multi-omics approaches to actively generate large-scale genomics datasets encompassing both normal and cancerous tissues from individuals across ages. We are seeking a motivated postdoctoral researcher to join our team and contribute to the analysis of extensive DNA and RNA sequencing datasets. Additionally, there is an opportunity to participate in the development of novel experimental, statistical, and computational methods that integrate multi-dimensional genetic data. The successful candidate will work closely with our interdisciplinary team, collaborating with experimentalists, clinicians, and computational scientists. This position offers a unique opportunity to be part of cutting-edge research in the field, exploring somatic mutations and their implications in normal and precancerous tissues. Teichmann Project - Genomic and computational dissection of tissue architectures Supervisor: Sarah Teichmann Contact: [email protected]

Establishment of endometriosis lesion-or- Using next-generation sequencing and ganoid screening platform high-throughput cellular phenotyping and Supervisors: Dr Roser Vento-Tormoand models to understand the biological basis and Dr Iva Kelava of inflammatory bowel disease Contact: [email protected] iva. Supervisors: Dr Carl Anderson [email protected] Contact: [email protected] Endometriosis is a common condition Our group has a long-standing interest in the characterised by the growth of endometrial genetics of inflammatory bowel disease (IBD). IBD tissue outside the uterus (called “lesions”). It is a chronic, debilitating disorder of the affects at least 10% of women of reproductive gastrointestinal tract that affects around 0.5% of age and is accompanied by many symptoms, the population, with a typical onset in early including pain and issues with conception. adulthood. Many IBD patients ultimately require Despite the high prevalence of the disease, major abdominal surgery, resulting in lifelong non-invasive diagnostic tests and efficient, disability, because an appropriate drug either well-tolerated treatments are almost completely does not exist or is not administered soon lacking. Current treatments are limited to surgical enough. Total healthcare costs in the UK are and/or hormone/analgesic treatment, both being estimated to be over £1 billion per year associated with high morbidity and significant (Cummings et al., 2008). Disease pathogenesis is side-effects. Therefore, there is an urgent unmet poorly understood but is likely driven by a clinical need for reliable non-invasive diagnostic dysregulated immune response to commensal tools and novel therapeutic approaches. Also, gut microorganisms in genetically susceptible there is a lack of knowledge of the cellular origins individuals. IBD is highly heritable and the group and composition of endometrial lesions. The has played a leading role in the identification of project is aimed to address those knowledge over 240 regions of the genome associated with gaps by using single-cell multiomics data disease susceptibility. These loci were produced by our team to generate a model of predominantly detected via genome-wide endometriosis lesions derived from patients. To association studies and are driven by common do so, we want to adapt current protocols to genetic variants. derive organoids from endometriosis lesions (see Together with our collaborators, we are recent publication by our team in Nature generating a number of large-scale genetic and Genetics) and establish co-culture conditions for genomic datasets and resources to better a robust multilineage organoid platform. The understand the biological basis of IBD development and validation of this system will susceptibility, disease progression and drug be invaluable for identifying new therapeutic response. These include: targets and performing drug-screenings. 1. Whole-exome sequencing data for almost In our work we combine state-of-the art 100,000 IBD patients and 500,000 population genomics technologies - single cell controls. 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.

2. Single-cell RNA sequencing data from gut characterise these species complexes - to test biopsies and blood samples from thousands of how well the genetic data corresponds to individuals, both with and without IBD. morphological species descriptions, and how the 3. Genome-wide CRISPR screens in primary increasing movement restriction with increasing immune-cells ascertained from individuals with depth affects the speciation process. This will and without IBD. require sampling the species at various locations 4. Mucosal organoids for hundreds of genotyped across the UK and potentially also mainland IBD patients. Europe, for whole genome population We’re keen to receive applications from resequencing complementing reference individuals who have a vision for using one or genomes already generated in the Jaron group. more of these datasets to help us deliver on our This project would suit applicants with an mission of building new therapeutic hypotheses interest in biodiversity and evolutionary and expediting personalized medicine for IBD. genomics, with potential implications for We’re also excited to hear candidate-driven questions regarding soil health and agriculture. project proposals that utilize the Sanger The postdoctoral fellow will be part of the Jaron Institute’s large-scale data generation platforms, and the Meier research groups, as well as part of and/or our established national network of a larger organisation - the Soil Invertebrate gastroenterologists for sample ascertainment Genome Initiative (SIGI). We are happy to provide and clinical input, to build novel datasets that can the applicant with all the necessary genomics be applied to deliver on these goals. The team and organismal training. currently consists of computational geneticists, Tree of Life – BIOSCAN and ANOSPP pro- cell biologists, computer scientists, ject opportunities immunologists and clinicians, and we are keen to Supervisor: Mara Lawniczak hear from applicants across this broad range of Contact: [email protected] backgrounds. Our group is surveying huge numbers of insects Speciation in soil arthopods using two different project – both of which use Supervisors: Kamil Jaron (genomics of targeted sequencing approaches to tell us what springtails) and Joana Meier (speciation species are where over space and time. These genomics) projects result in incredibly rich biobanks of DNA Contact: [email protected] joana. poised for more research. [email protected] BIOSCAN is focused on the UK – we have dozens Soil arthropods are as much, or perhaps even of partners around the country now operating more, species rich than other organism groups, monthly Malaise traps and operating monthly yet very little is known about how they speciate. Malaise traps and sending us 96-well plates of Soil is a very stable environment, but restricts specimens. movement of creatures living in it. These are factors that are expected to affect the speciation process and make soil organisms an interesting contrast to the typical study systems for speciation which are all above-ground or aquatic organisms. In this proposal we focus on springtails (Collembola), which together with mites make up a vast majority of soil arthopods. They are a diverse clade occupying all parts of the soil gradient. We propose to select three distantly related springtail genera at different depths in the soil. Good candidates would be Dicyrtomina, Entomobrya and Megalothorax. We propose to

We use just 0.1% of the DNA that we non- destructively extract to DNA barcode each specimen. This postdoc fellowship could be focused on doing interesting and important science using the remaining 99.9% of the DNA for a subset of the 1000s of specimens we evaluate each month. For example, genomic explorations of key pests or pollinators found among the samples or dives into species complexes using whole genome sequencing. ANOSPP is focused primarily on the diversity of Anophelines across Africa and investigating evidence of malaria transmission among these species. ANOSPP partners have shared specimens and thus DNA for many secondary vectors (e.g. Anopheles coustani, marshallii, nili). We want to begin exploring the population structure of these other malaria vectors similarly to what we have completed for Anopheles gambiae (see 2017 paper) and what we are working on now for Anopheles funestus. Both of these projects would suit someone with a strong interest in entomology, ecology, genomics and with a desire to make a difference in conservation (BIOSCAN) or infectious disease (ANOSPP). We would be delighted to work with you to design a fellowship project in the general areas described above to suit your specific interests.

Equality, in our sector and we are committed to doing Diversity and what we can to correct this. We positively Inclusion encourage applications from candidates regardless of sex, race, disability, age, sexual Our global reputation for excellence is orientation, gender reassignment, religion or strengthened by our commitment to developing belief, marital status, or pregnancy and maternity and maintaining a positive, fair and healthy status. working environment – our Equality, Diversity For more information about EDI at GRL see our and Inclusion (EDI) Programme is about valuing Equality in Science Programme. our people and supporting them to be their best. Our leaders play a key role in nurturing a positive Our strength lies in the diversity of our and inclusive culture where everyone can thrive people, skills and ideas.” and diversity is celebrated. We have developed an ambitious programme of activity that drives organisational culture change, empowers our leadership and ensures that equity and inclusion principles are embedded across all of our processes – from recruitment, promotion, reward, to accessing career development opportunities In order to further reinforce our commitment to being a fully inclusive workplace, we became Stonewall Diversity Champions in 2020 to support LGBT+ inclusion. We are also signatories of the Race at Work Charter and Disability Confident scheme and are working towards these principles. Our broader Wellcome Genome Campus-wide EDI initiatives include our LGBT+, Race Equity, Neurodiversity and Parent and Carers’ Staff Engagement Networks. These bring people together, raise awareness, provide specific and relevant support and development opportunities and are safe spaces for people to be themselves. We are committed to providing equal opportunities for everyone, regardless of their background. We acknowledge that people from certain backgrounds are under-represented