Open Targets is an innovative, public-private partnership that uses human genetics and genomics data at large scale for systematic drug target identification and prioritisation.
We apply two general and interconnected approaches:
Systematic, high throughput experimental projects in human, physiologically relevant systems to generate new data on the causal links between targets and diseases in our focus therapeutic areas
Integration of publicly available evidence that associates targets with disease in our informatics programme, exemplified by the Open Targets Platform and the Open Targets Genetics Portal
Open Targets brings together expertise from seven complementary institutions including the Wellcome Sanger Institute, EMBL-EBI, GSK, Biogen, Celgene, Sanofi and Takeda. We combine world-class scientific expertise of the Sanger Institute with scientific and translational input from industry to develop the Open Targets research programme.
The Open Targets Research Programme
We enable Sanger Scientists to work collaboratively with our industry partners to develop and execute ambitious projects with a focus on drug target identification and prioritisation. We encourage cutting-edge approaches that capitalise on new technologies and enable systematic approaches to yield target lists at large scale. We regularly issue calls for new project ideas but are always open to discussing new project ideas together.
In our Experimental programme we focus on three core therapy areas where the overlap of interest and expertise across our partners is strongest. We will consider excellent projects outside these therapy areas where there is sufficient interest from our partners.
In our Informatics programme we are interested in approaches to integrate, analyse and visualize data across all types of human disease to enable drug target identification and prioritisation.
Our Core Therapy Areas
Inflammation & immunity
We are interested in the role of the immune system in disease and how it could be modulated to treat disease. Initial Open Targets projects probed the role of targets in well-defined immune cells through gene editing and epigenetic profiling (for instance in macrophages, dendritic cells, T cells and regulatory T cells in response to various stimulations). Newer projects are refining how we can interpret hits from GWAS by mapping eQTLs in cells and tissues relevant to immune disease and exploring the functional consequence of variants and gene perturbation in more complex models of disease. We have an interest in projects in immuno-oncology and exploring the role of the immune system in neurodegeneration in line with our other core therapy areas.
We are interested in the vulnerabilities of cancer and finding new targets to treat cancer directly or by harnessing the immune system. We work strategically with the Cancer Dependency Map and the resources and expertise within Sanger to work at the forefront of research to understand the genetic basis of cancer. We use a variety of accessible cancer resources to curate and analyse clinical genomic datasets to identify driver genes (mutations, amplification, deletions and gene-fusions) across multiple cancer sub-types. We use genomic and other ‘omic information to establish the disease relevance of the cancer cell lines, enable the selection of model systems that best reflect the biology of tumours and identify clinically relevant associations. In increasingly complex systems we are systematically perturbing the genome to reveal new targets and new target combinations.
We are interested in the causes of neurodegeneration across a range of diseases with important unmet need. We work with experts at Sanger and third parties such the UKDRI using approaches such as gene editing in neurons derived from iPS cells to identify modifiers of the responses to oxidative stress, mechanisms of Tau uptake and the effects of Alzheimer’s disease specific mutations. We are using fine mapping of GWAS in Alzheimer’s and Parkinson’s disease to identify and test potential targets in the same neuron systems. We also capitalise on the established expertise at the Sanger Institute to characterise these systems and their perturbations at the single-cell level using the latest in single-cell genomics technologies.
We partner with groups at the Sanger Institute to deliver experimental and informatics projects as part of our research programme. Additionally, Sanger contributes to core Open Targets teams such as the Genetics Team and the Validation Lab. Our flagship platforms are the Open Targets Platform and the Open Targets Genetics Portal. Other resources that we have developed through our collaborative research include Project Score,epiChoose, CRISPRcleanR,CELLector (Genomics Guided Selection of Cancer in vitro Models), LINK (LIterature coNcept Knowledgebase) and DoRothEA (Discriminant Regulon Expression Analysis). Further details of our publications to date and our research resources can be found on our website.Details on our resources can be found on our website.
We partner with various groups at the Sanger Institute across our multidisciplinary research programme. Sanger staff are integral to our core teams in Genetics and in the Validation Lab.
The goal of our reseach is to use high-throughput screens to gain causal insights into the biological basis of human disease, identify new drug targets and determine the patients who will benefit most from these drugs. We focus on immune-mediated disease, and inflammatory bowel disease in particular, due to the significant burden of disease and the accessibility of disease relevant tissue.
We are a team of cancer biologists, geneticists and computational biologists interested in understanding how cancers develop and the ways of controlling their growth. We work on a range of malignancies but are particularly interested in melanoma and other skin cancers.
Gene expression involves the transformation of genetic information encoded in DNA sequence into a gene product, such as a protein. Regulation of gene expression is a fundamentally important process in biology because controlling the timing, location and level of gene expression is critical for the gene product to function correctly. The majority of mutations that alter disease risk for most common diseases are thought affect gene regulation, although how these mutations actually function is not well understood in most cases. Our group uses a combination of statistical and experimental approaches to map mutations that affect gene regulation in humans.
The Hemberg group is interested in developing quantitative models of gene expression. Our approach is theoretical and we strive to develop novel mathematical models as well as computational tools that can be used by other researchers.
Our group studies how normal cell behaviour is altered by mutation in aging and the earliest stages of cancer development. We focus on normal skin epidermis and the lining of the oesophagus which acquire a high burden of mutations by middle age. Our approach combines deep sequencing of normal human tissues with transgenic mouse models, novel 3D culture methods, gene editing, live imaging, single cell analysis and quantitative modelling. We have disccovered that normal tissues are extensively colonised by mutant cells. Some mutations increase cancer risk while others may decrease it. We are now researching how to redirect evolutionary selection to reduce the burden of the most deleterious mutations.
Our goal is to understand how genetic background influences outcome of mutations. To do so, we measure, model, and modulate cell state across healthy and disease-relevant human genetic diversity. In the lab, we develop tools for genetic perturbations, and use genome engineering and synthetic biology to create cell lines for screening cellular traits. In the office, we develop probabilistic models as well as software tools to accurately and efficiently analyse the readouts.
We develop novel genome editing techniques, cellular differentiation and cellular phenotyping systems, especially with respect to high-throughput investigation of gene and non-coding regulatory element function.
We use cutting edge single cell genomics technologies and computational methods to understand genes, proteins and cells in human health and disease. We have a long-standing interest in understanding global principles of gene regulation, protein interactions and have a particular interest in immunity.
Our research focuses on the application of large-scale genomic analysis to unravel the spectrum of human genetic variation associated with cardiometabolic diseases, and its interaction with non-genetic and environmental cues.
The host-microbiota Interactions laboratory studies the mechanisms that underlie how micro-organisms in the gut, nasopharynx and uro-gential tract interact with their host during periods of health and disease. In particular the team seek to develop novel ways to treat diseases that are associated with unwanted imbalances in the micro-organism population.