Janet Thornton Fellowship

Janet Thornton Fellowship

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.

The 2018 call is now open click here to apply
fellows.jpgSanger 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.

What's included?

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:

  • Salary £31,503 - £39,492
  • 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

One Janet Thornton Fellowship is awarded each year following a competitive selection process.

If you have questions about what is included in the Fellowship please email saher.ahmed@sanger.ac.uk

Eligibility

The Janet Thornton Fellowship is open to scientists who:

  • have had a break from scientific research, of 12 continuous months or more, for any reason
  • are not currently working in scientific research
  • have at least one years' postdoctoral experience

The closing date for applications is Friday 29 June 2018

Click here to apply

If you have questions about your eligibility for the Fellowship please contact saher.ahmed@sanger.ac.uk.

Anderson project

Anderson Project - Using next-generation sequencing to understand inflammatory bowel disease
Supervisor: Dr Carl Anderson
Contact: ca3@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 requiring 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 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.

As part of the UK IBD Genetics Consortium we are currently whole-genome sequencing over 8,000 IBD cases and 12,500 population controls to powerfully test the entire allelic spectrum for association to IBD. In hundreds of healthy individuals, we are using single-cell RNA sequencing of gut biopsies to identify eQTLs in across the entire population of cells in the gut. We will use these eQTLs to identify potential therapeutic targets within IBD associated loci. In our wet lab we are performing high-throughput CRISPR knockout screens in disease relevant cells to identify causal genes and elucidate the cellular mechanisms underpinning IBD. We are seeking a Janet Thornton Fellow play a leading role in least one of these projects. We are also keen to hear research ideas from potential fellows that are aligned with our research goal of using high-throughput genetics and genomics to better understand the pathogenesis of immune-mediated diseases such as IBD and primary sclerosing cholangitis.

Davenport Project

Davenport Project - Integrating functional genomics and clinical datasets to understand drug response heterogeneity
Supervisor: Dr Emma Davenport
Contact: edaven@broadinstitute.org

When a group of patients are treated with a drug, there can be substantial heterogeneity in their response to treatment including serious adverse effects. Understanding this heterogeneity is necessary to improve patient stratification for precision medicine based approaches to treat disease.

We hypothesise that genetic regulators of gene expression are one of the key sources of variability in drug response. We integrate functional genomics and clinical datasets to understand how regulatory variants interact with drug exposure. We have recently developed a statistical framework for identifying expression quantitative trait locus (eQTL) effects that are modulated after treatment with a drug (drug-eQTL interactions, bioRxiv doi: 10.1101/118703). We are now focusing on combining computational and wet lab approaches to identify the genetic variants driving eQTL interactions, to understand the molecular mechanisms and cell types through which they are acting and ultimately determine how regulatory variants are contributing to drug response heterogeneity.

Ellis project

Ellis Project - Developing and Employing CapTF Synthetic Sponge DNA Arrays
Supervisor: Dr Tom Ellis (Associate Faculty in Synthetic Genomics)
Contact: t.ellis@imperial.ac.uk

The classic model of transcription factor (TF) action sees the TF protein randomly diffuse to promoter DNA and bind tightly upon recognition of the DNA bases of its binding site motif. This is thought to occur for over 1000 TFs as they locate their targets in the 6 billion bases of the human genome. However, in reality most TFs are promiscuous, binding to many sequences that are broadly similar to their main target. Recent work in bacterial synthetic biology has exploited the promiscuity of TFs, by making synthetic DNA intentionally designed to be bound by TFs and using this DNA to titrate TFs away from their usual target when needed - effectively soaking them up like a sponge.

Here we plan to extend this approach and use it to understand promiscuous TF binding around the human genome, in the hope of quantifying how much TF binding occurs in non-promoter DNA regions. We will use synthetic DNA library generation to create Capture Transcription Factor (CapTF) Synthetic Sponge DNA Arrays. We will design and synthesise an array for each human TF, making around 1000 of these in parallel to get a library representing all known human TFs. These arrays will consist of tandem repeats of the predicted strong binding sites for the TF plus a barcoded region that is actively transcribed. The array plasmid library will be pooled and transfected into human cells (e.g. iPSCs) and the perturbation of gene expression from the action of each CapTF sponge array will be determined from single cell RNAseq measurements. The data from the CapTF experiment will be used to build a model of the levels of each TF in the cell and the anticipated number of off-target sites they usually bind around the human genome (e.g. within ‘junk’ DNA). Understanding the numbers of these sites and their necessity will be essential for future efforts that seek to recode, rearrange and reduce the human genome.

Lawley Project

Lawley Project - Impact of early life microbiota colonisation on long-term health and development
Supervisor: Trevor Lawley, Host-Microbiota Interactions Lab
www.lawleylab.com
Contact: trevor.lawley@sanger.ac.uk

At birth, newborn infants experience rapid colonisation by microorganisms, including those acquired from their mother, representing an unappreciated form of kinship. Microbial colonisation at birth is a critical life event that is thought to have major effects on a child’s subsequent development, immune system and health. Perturbation of microbiota inheritance by such factors as caesarean section, antibiotic exposure and preterm birth are epidemiologically linked to a growing number of diseases and syndromes such as necrotizing enterocolitis, asthma, type 1 diabetes, obesity and eczema.
The Lawley Lab forms part of the Baby Biome Study, an innovative interdisciplinary birth cohort study which aims to track the lives of up to 40,000 UK infants and their parents through pregnancy, birth and their early years. We are collecting paired mother and infant biological samples (including faeces and cord blood) to create an internationally unique and future-proofed biorepository. The Lawley Lab is leading the microbiota analysis with access to the biorepository, with linked demographic, clinical and other data for Baby Biome participants. To date, we have performed metagenomic sequencing and analysis of 1683 stools collected from a longitudinal birth cohort of 777 term infants and mothers from three UK hospitals. We have also performed deep culturing and sequencing from stool, creating a culture collection available for follow up functional and mechanistic studies.
This project offers an outstanding opportunity to explore the long-term effects of infection and immune development on human disease processes, at a scale and scientific depth never performed before. This proposed Thornton Fellowship project could easily be crafted for either computational biology project or a lab-based project, or contain elements of both. The Thornton Fellowship will benefit from having access to a variety of techniques and concepts including metagenomic analysis pipelines and resources, mouse models (transgenic and germ-free mice), comparative genomics/proteomics, pathogen biology and anaerobic microbiology

Parts Project

Parts Project – Mapping the robustness and determinants of gene functions
Supervisor: Dr Leopold Parts
Contact: lp2@sanger.ac.uk

Genes do not function the same way in different individuals. This variability is caused by genetic modifiers scattered throughout the genome, and environmental ones modulating the cells in non-heritable ways. Few of the causes have been identified in mammals, and therefore we know little about their mechanisms of action or general properties. We propose for the first time to map the robustness and determinants of gene function in many healthy humans.

To achieve this, we are in the process of generating Cas9 carrying induced pluripotent stem cell (iPSC) lines from healthy donors in the HIPSCI cohort. We will treat these lines with a lentiviral library targeting all genes in the genome, to obtain large cell populations with deletions in one of the genes. This will already give us an estimate of the malleability of gene function; in this project, we propose to extend the analysis to genes' other roles as well. To measure gene function, we will fix and permeabilize the cells, and stain them with antibodies that reflect the gene property we want to analyse, e.g. signaling pathway activity. Finally, we will sort the cells according to the staining signal to understand which genes are required for wild type function, and how this requirement changes across different genetic backgrounds.

Rayner Project

Rayner Project - High throughput genetic approaches to Identify targets for new antimalarial drugs
Supervisor: Dr Julian Rayner
Contact: jr9@sanger.ac.uk

Plasmodium falciparum, a single celled eukaryotic parasite, still causes more than 250 million cases of malaria each year, and approximately 500,000 deaths. With no effective vaccine malaria control relies entirely on insecticides and antimalarial drugs, both of which are threatened by resistance. Parasites resistant to artemisinin, the current frontline antimalarial, have recently emerged in Southeast Asia and are spreading rapidly. In the past when such drug resistant parasites have reached Africa, where the majority of malaria mortality occurs, they have caused millions of deaths.

There is therefore an urgent need to identify new antimalarial drugs to replace artemisinin. High throughput screens by a number of pharmaceutical companies have identified hundreds of hit compounds, but to develop these hits into drugs, their targets within the Plasmodium genome need to be identified.

At the Sanger Institute the Plasmodium Genetic Modification Project, PlasmoGEM, is scaling up experimental genetic approaches to understand malaria parasite biology and to identify and prioritise new drug targets. Combining genetics with nextgen sequencing in a parallel phenotyping approach (PMID: 25732065), we have recently performed the first genome-scale knockout screen in Plasmodium parasites (PMID: 28708996). We are now performing additional gene knockout screens to investigate areas of Plasmodium biology ranging from sexual differentiation to host cell invasion, but the same fundamental technology could be used to identify the targets for these new hit compounds.

This chemogenomic approach, which combines systematic over-expression screens with drugs or other compounds, has been used extensively in model organisms such as yeast but never previously in malaria parasites. The project would establish the chemogenomic methodology by developing barcoded overexpression vectors and exploring their ability to be transfected in large pools and quantified using nextgen sequencing. They would then work with industrial partners to apply the technology to identifying targets for lead compounds, thereby playing a key role in developing much-needed new antimalarial drugs.

Working as part of a multidisciplinary research team at the Sanger Institute, the candidate would gain valuable and highly transferrable experience in eukaryotic cell biology, large scale genetic approaches, drug development and genomics.

Teichmann Project

Teichmann Project - Genomic and computational dissection of tissue architectures
Supervisor: Sarah Teichmann
Contact: st9@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.

Contact

Please send any queries about the Janet Thornton Fellowship to saher.ahmed@sanger.ac.uk