Wellcome Sanger Institute
|Location||Hinxton, Cambridgeshire, United Kingdom|
|Address||Wellcome Genome Campus|
The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust.
It is located on the Wellcome Genome Campus by the village of Hinxton, outside Cambridge. It shares this location with the European Bioinformatics Institute. It was established in 1992 and named after double Nobel Laureate, Frederick Sanger. It was conceived as a large scale DNA sequencing centre to participate in the Human Genome Project, and went on to make the largest single contribution to the gold standard sequence of the human genome. From its inception the Institute established and has maintained a policy of data sharing, and does much of its research in collaboration.
Since 2000, the Institute expanded its mission to understand "the role of genetics in health and disease". The Institute now employs around 900 people and engages in four main areas of research: Human genetics, pathogen genetics, mouse and zebrafish genetics and bioinformatics.
Facilities and resources
In 1993 the then 17 Sanger Centre staff moved into temporary laboratory space at Hinxton Hall in Cambridgeshire. This 55-acre (220,000 m2) site was to become the Wellcome Genome Campus, which has a growing population of around 1300 staff, approximately 900 of whom work at the Sanger Institute. The Genome Campus also includes the Wellcome Trust Conference Centre and the European Bioinformatics Institute. A major extension of the campus was officially opened in 2005; the buildings accommodate new laboratories, a data centre and staff amenities. In discussing the name of the centre, Sanger (still alive when the centre was opened) told John Sulston, the founding director, that the centre "had better be good." Sulston commented, "I rather wished I hadn’t asked."
The Sanger Institute's sequencing staff handle millions of DNA samples each week. The Institute "capitalises on leading-edge technologies to answer questions unanswerable only a few years ago". The advances in technology allow the Sanger Institute to carry out sequencing of the genomes of individual humans, vertebrate species and pathogens, at an ever-increasing pace and reducing cost. The Institute has more than 100 ongoing pathogen sequencing projects. The output of the Sanger Institute is around 10 billion bases of raw sequence data per day.
Bioinformatic databases resources are one of the outcomes of research programmes that the Sanger Institute is involved in. Those hosted by the Sanger Institute include:
- COSMIC, a catalogue of somatic mutations in cancer
- DECIPHER, a database of chromosomal imbalance and phenotype in humans, using Ensembl resources
- Ensembl, a genome browser co-hosted by the European Bioinformatics Institute.
- GeneDB, a pathogen sequence database
- MEROPS, a peptidase database
- Mouse Genetics Project, including a database of standardised phenotypic analysis for many hundreds of mutant mice.
- Pfam, a protein family database
- Rfam, an RNA family database
- TreeFam, a database of phylogenetic trees for animal genes
- Vega, a vertebrate genome annotation resource
- WormBase, a database on the biology and sequence of the model organism C. elegans and other related Nematodes.
- WormBase ParaSite, a database for the genomics for parasitic helminths (both Nematodes and Platyhelminthes).
Since 2000, the Sanger Institute has built on its sequencing skills to develop new programmes in postgenomic biology - understanding the messages in genes. As of 2016 (when the Institute's latest 5-year funding plan began), the Institute engages in several areas of research:
Cancer, Ageing and Somatic Mutation Programme
Provides leadership in data aggregation and informatics innovation, develops high-throughput cellular models of cancer for genome-wide functional screens and drug testing, and explores somatic mutation's role in clonal evolution, ageing and development.
Cellular Genetics Programme
Explores human gene function by studying the impact of genome variation on cell biology. Large-scale systematic screens are used to discover the impact of naturally occurring and engineered genome mutations in human induced pluripotent cells (hIPSCs), their differentiated derivatives and other cell types. It is one of the founder programmes driving the creation and organisation of the international Human Cell Atlas initiative.
Human Genetics Programme
The Institute's research in human genetics focuses on the characterisation of human genetic variation in health and disease. Aside from the Institute's contribution to the Human Genome Project, researchers at the Sanger Institute have made contributions in various research areas relating to disease, population comparative and evolutionary genetics. In January 2008, the launch of the 1000 Genomes Project, a collaboration with scientists around the globe, signalled an effort to sequence the genomes of 1000 individuals in order to create the "most detailed map of human genetic variation to support disease studies". The data from the pilot projects was made freely available in public databases in June 2010. In 2010, the Sanger Institute announced its participation in the UK10K project, which will sequence the genomes of 10,000 individuals to identify rare genetic variants and their effects on human health. The Sanger Institute is also part of the International Cancer Genome Consortium, an international effort to describe different cancer tumour types. It is also part of the GENCODE and ENCODE research programmes to create an encyclopaedia of DNA elements.
The Programme applies genomics to population-scale studies to identify the causal variants and pathways involved in human disease and their effects on cell biology. It also models developmental disorders to explore which physical aspects might be reversible.
Infection Genomics Programme
Investigates the common underpinning mechanisms of evolution, infection and resistance to therapy into bolster understanding of bacteria, viruses and parasites. It also explores the effects of genome variation on the biology of host-pathogen interactions, in particular host response to infection and the role of microiotia in health and disease. All the genomes after sequencing are made available at the web-based onsite-maintained database, GeneDB.
Integrates genomic, genetic and proteomic approaches to develop and enhance high-throughput tools and technologies to study specific biological problems relevant for malaria control and to understand the fundamental science of the human host, the mosquito vector and the Plasmodium pathogen.
All of this research is underpinned by expertise in a number of key areas:
The Sanger Institute's bioinformatics teams have developed IT systems for sequencing and postgenomic research. The Institute houses genome resources, RNA, protein and other family resources and functional annotation databases and resources. Researchers worldwide are able to use these resources to make inferences of genomic knowledge through computational analysis and integration of data.
Mouse and zebrafish teams at the Sanger Institute enable Sanger researchers to explore the genome sequences of these model organisms to understand basic biological mechanisms, and gene function in human health and disease. Project supported include the study of development, cancer, hearing and behaviour.
Experimental biological models
With the creation of the Sanger Institute-EBI Single Cell Centre and the Cellular Generation and Phenotyping]pipeline, the Institute has developed state-of-the-art human induced pluripotent stem cell, induced pluripotent stem cell, single cell and organoid facilties to deliver the next generation of biological models.
Much of the Sanger Institute's research is carried out in partnership with the wider scientific community; over 90 percent of the Institute's research papers involve collaborations with other organisations. Significant collaborations include:
- 1000 Genomes Project
- GENCODE and ENCODE (ENCyclopedia Of DNA Elements)
- International Cancer Genome Consortium
- International HapMap Project
- International Knockout Mouse Consortium
- International Mouse Phenotyping Consortium
- SNP (Single nucleotide polymorphism) Consortium
- The Copy Number Variation Project
- The genome sequencing of S. pombe, C. elegans, mouse and the Malaria parasite.
- The Human Genome Project
- The UK 10,000 Genomes Project (UK10K)
- Wellcome Trust - Department of Biotechnology, India Alliance
The Sanger Institute has a programme of public engagement activity. The programme aims to make complex biomedical research accessible to a range of audiences including school students and their teachers, and local community members.
The Communication and Public Engagement programme aims to "encourage informed discussion about issues relevant to Sanger Institute research" and "foster a community of researchers who can engage effectively with different audiences". The Institute hosts visits for more than 1,500 students, teachers and community groups per year. Visitors may meet scientific staff, tour the Institute and its facilities, and participate in ethical debates and activities. The programme also offers professional development sessions for teachers of GCSE and post 16 science through the national network of Science Learning Centres, and by hosting visits for groups interested in updating their knowledge in contemporary genetics. Videoconferencing into the Sanger Institute is also offered for Science Learning Centres, Science Centres and schools.
The programme maintains a dedicated public website, yourgenome.org, that is intended to help people understand genetics and genomics science and its implications for society. The website includes teaching resources for secondary school science teachers that have been developed with Institute researchers.
Scientific and public engagement staff also collaborate on and contribute to national projects such as the UK's InsideDNA traveling exhibition and the Who am I? gallery at The Science Museum. They also participate in public events such as the Cambridge Science Festival.
The Institute operates two PhD training programmes: a four-year course for basic science graduates, and a three-year course for clinicians. The four-year course requires students to rotate around three different laboratories in order to broaden their scientific horizons before choosing a PhD project. Each student is required to choose at least one experimental and one informatics-based rotation project. Institute houses approximately 50 pre-doctoral students, all of whom are registered at the University of Cambridge.
Allegations of bullying
On the 29 august 2018, it was reported that key staff in the institute including Michael Stratton were under investigations for allegations of staff being mistreated and bullied. Furthermore it was alleged that scientists were pressured to leave the institute and such treatment had disproportionately affected female staff.
As of 2015 a faculty of 42 scientists lead hypothesis-driven research, seeking answers to biomedical questions. These include:
- Allan Bradley FRS- Mouse genomics
- Peter Campbell - Cancer Genome Project
- Gordon Dougan FRS - Microbial pathogenesis
- Richard Durbin FRS - Genome informatics
- Dominic Kwiatkowski FRS parasites and microbes programme
- Ultan McDermott - Cancer Genome Project
- Julian Parkhill FRS - Pathogen genomics
- Julian Rayner - Malaria
- Michael Stratton - Cancer Genome Project
- Sarah Teichmann - Gene expression genomics
- Eleftheria Zeggini human genetics
Associate faculty and international fellows
Associate Faculty members work part-time at the Sanger usually jointly with another organisation. As of 2015 there are 16 associate faculty including:
- Adrian Bird FRS - Epigenetic mechanisms in health and disease, Professor at the University of Edinburgh
- Ewan Birney FRS, based at the European Bioinformatics Institute
- John Danesh, Professor in the Department of Public Health and Primary Care at the University of Cambridge
- Chris Ponting - Computational genome biology, based at the University of Oxford
- Fiona Powrie, FRS, University of Oxford
- Stephen O'Rahilly, Professor at the University of Cambridge
- Wolf Reik - Epigenetic reprogramming, based at the Babraham Institute
- Toni Vidal-Puig, Professor of Molecular Nutrition and Metabolism at the Institute of Metabolic Science, University of Cambridge
Scientific Advisory Board
The Sanger Board of Management are guided by the scientific advisory board whose members include Professor David Altshuler, Professor Anton Berns, Professor David J. Lipman, Professor Kevin Marsh and Professor Sir Paul Nurse.
John E. Sulston was the founding Director of the Sanger Institute. Sulston was instrumental in the choice of the Hinxton site for the Institute and remained there as Director until the announcement of the completion of the draft human genome in 2000. Sulston graduated from the University of Cambridge in 1963 and completed his PhD on the chemical synthesis of DNA in 1966. He shared the 2002 Nobel Prize in Physiology or Medicine with Robert Horvitz and Sydney Brenner, two years after standing down as Director of the Institute.
In 2000, Allan Bradley left his appointment as Professor at the Baylor College of Medicine, in the USA, to take up the position as Director of the Sanger Institute. Bradley wanted to build on the achievements made by the Sanger Institute in the Human Genome Project by "concentrating on gene function, cancer genomics, and the genomes of model organisms such as the mouse and the zebrafish". Bradley received his BA, MA and PhD in Genetics from the University of Cambridge.
In 2010, Bradley stepped down from his leadership role to form a startup company, but remains on the faculty of the Institute as Director Emeritus. Mike Stratton, who is a leader of the Cancer Genome Project and the International Cancer Genome Consortium, was appointed Director of the Sanger Institute in May of that year.
The Wellcome Trust Sanger Institute was established in 1992, funded by the Wellcome Trust and the UK's Medical Research Council. One of the primary goals of the Institute on its creation, was to "play a role in mapping, sequencing and decoding the human genome and the genomes of other organisms". The Sanger Institute now hosts several research programmes aiming to elucidate the associations between genes and biological traits - most often disease susceptibilities. The Sanger Institute has, since inception, maintained a policy that "aims to provide rapid access to data sets of use to the research community".
Organizational and company spin outs
The company Congenica was spun out of the Institute in the early 2000s to commercialize a clinical genetics analysis and reporting technology developed at the Institute, technology instantiated in Congenica's Sapientia platform. Sapienta is used in several large scale genome intrepretation projects, including 100,000 Genomes Project. Congenica is based at the Welcome Genome Campus, and completed a round of Series B financing in 2017.
Human Genome Project
The Sanger Institute was opened in 1993, three years after the inception of the Human Genome Project, and went on to make the largest single contribution to the gold standard sequence of the human genome, published in 2004. The Institute was engaged in collaborations to sequence 8 of the 23 human pairs of chromosomes (1, 6, 9, 10, 13, 20, 22, and X). Since the publishing of the human genome, research carried out at the Institute has developed beyond sequencing of organisms into various biomedical research areas, including studies into diseases such as cancer, malaria and diabetes.
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