Wellcome Trust Sanger Institute moves to new era
The Institute, which is sequencing one-third of the human genome, enters a new era under the leadership of director, Dr Allan Bradley.
The new post-genomic period builds on the Institute's groundbreaking work in sequencing the human genome. In addition, genomes from tens of disease-causing organisms (pathogens), including the malaria parasite, are being sequenced. Teams of scientists at the Institute will now determine how genes build and control the human body. They will also study the roles that human and pathogen genomes play in health and disease.
The Institute's expenditure for 2001-2002 will be £63.3 million, one third of which will be used for new projects, paving the way for a new generation of health advances.
"This is what we call big science. The Wellcome Trust Sanger Institute will continue to make an enormous contribution to the international Human Genome Project. The Director Allan Bradley, a true scientific visionary, will now lead the Institute into the post-genomic era. As well as doing its own world-class research, the Institute will produce biological resources that will be of unparalleled importance to the scientific and medical communities. It will continue its tradition of giving these groups the resources they need to bring about healthcare advances for diseases like cancer, heart disease and diabetes."
Dr Mike Dexter, Director of the Wellcome Trust
"These new initiatives will complement and build on the Institute's considerable strengths in genome data generation, automation and bioinformatics."
"The new funding will allow the Wellcome Trust Sanger Institute to make a contribution to global science and medicine as significant as its contribution to the Human Genome Project. We will bring biology to the genome and translate the enormous amount of information encoded in our DNA into an understanding of gene function, providing the stimulus for real healthcare advances."
Dr Allan Bradley, Director of the Wellcome Trust Sanger Institute
Core Projects: Human Genomics and Genetic Studies in Model Organisms
The world's largest cancer genome study, headed by Professor Mike Stratton, will receive funding of up to £36 million over five years to search for genetic mutations that cause the most common cancers, including breast, lung, colorectal, ovary and prostate cancer.
"Our goal is to identify large numbers of new genes that are mutated in cancer and to measure the frequency of mutations in every major cancer. There are more than 100 different types of cancer, but we need to understand what makes them all different. This information will then be used to develop new, more specific drugs for improved treatment. The scale of the Cancer Genome Project is without match anywhere in the world."
Professor Stratton Mike Stratton, leader of the Cancer Genome Project at the Sanger Institute
The first phase of the Cancer Genome Project has already identified more genome abnormalities, ie. deletions or gaps in genetic information, in cancer cells than all previous studies combined. More than 80 of these genomic 'addresses' have so far been found and the study team are currently identifying the relevant cancer genes that would be located in these deletions. This research is expected to lead to the identification or many new tumour suppressor genes (ie. those genes which normally suppress tumour growth).
A new project aims to identify genes on the X chromosome (one of two sex chromosomes, of which women have two copies and men one) that give rise to the wide variety of disorders, using techniques employed for the Cancer Genome Project. The X-linked disease project will initially be used to search for genes involved in primary or nonspecific X-linked mental retardation, one of the most common disorders presenting at genetic clinics. Affected individuals have cognitive impairment but do not have any distinctive clinical or biochemical features in common.
The Institute will also focus on uncovering the basis of disorders that have multiple genetic contributions, including diabetes, asthma and other allergies. This will be achieved using a complete finished human genome sequence with all exons (or protein-coding regions) annotated, and a high-density map of single nucleotide polymorphisms (SNPs), small single-letter differences in the genome alphabet that make us all individuals. Understanding SNPs will help researchers understand why certain people are more susceptible to diseases than others, and why some respond well to certain drugs whilst others do not.
Common SNPs will be identified in all exons of the genome, and in collaboration with other groups, a map of common haplotypes in each gene will be produced, and the association between common haplotypes and disease will be determined.**
Genetic Studies in Model Organisms
Over the next five years, the Institute will initiate study of mouse models of disease, complementing work in other top genome research centres across the world, and other biomedical centres in the UK.
Mice provide the most suitable subjects to study many diseases common in humans, as mice share many aspects of early development, reproduction, and basic organ systems with humans. Every human gene has a mouse counterpart and 85% of their gene sequences are shared. The strong similarities between the genomes of the two species means that discoveries in one are often informative to the other.
The mouse genome is being sequenced by an international consortium; the Institute is responsible for sequencing 20% of the genome, and the project is due for completion in 2005.
A major programme of research in mouse and rodent models of disease will look for genes involved in repair of DNA damage - which are implicated in hereditary forms of colon and other cancers - and genes that are mutated or have altered activity in breast cancer. This knowledge will improve understanding of molecular pathways leading to cancer, and to potential new therapies.
The zebrafish genome provides a powerful tool to interpret the human genome, and the Wellcome Trust Sanger Institute began sequencing the zebrafish genome earlier this year. Sequencing projects around the world have already led to the identification of zebrafish genes involved in the development and function of organs such as heart, ear and kidney. The Institute is expected to complete sequencing of the zebrafish genome by 2005.
Studies will also continue in other model organisms such as yeast, and Caenorhabditis elegans (the round worm) to provide information on other biological pathways.
The Five-Year Strategic Plan
Genomics will drive forward progress in biological sciences and medical advances for many years to come, enabling the Trust to build upon the investment it made in funding the sequencing of the human genome and fulfil its mission to improve human and animal health. The new strategic plan will maintain the Wellcome Trust Sanger Institute at the forefront of the worldwide effort to translate gene sequences into real healthcare benefits.
The key elements of the strategic plan are:
Adding value to the genome sequence (genome annotation) to:
- Identify all the genes within the human genome
- Find the regions of the genome that control whether genes are turned on or off
- Compare the human genome with the genomes of model organisms such as mouse and zebrafish
- Find out where and when genes are expressed in the body - during development and in adult tissues
- Identify disease-causing genes in pathogens
- Predict the functions of genes
Bringing biology to the genome will:
- Establish biological and genetics programmes focused on human disease and model organisms; these programmes will be underpinned by the information from genome annotation
- Identify genetic mutations or variations that cause or increase the risk of human disease through programmes such as the Cancer Genome Project and a new X-linked Disease Project
- Establish a genetics programme to understand the role of genes in mouse development and physiology, and in human disease
- Gain further insights into the biology of pathogens and identify targets for antibiotics
Genome infrastructure will:
- Establish banks of biological materials to aid high-throughput research
- Develop new high-throughput technology
- Enhance the core computer technology - bioinformatics - to analyse and interpret the vast amounts of data the projects will produce
New opportunities for top researchers:
- Recruit 20 world-class investigators to lead independent research programmes
- Investigators will range from junior fellows at the early stages of their careers to principal investigators of international renown
- Establish postgraduate and postdoctoral programmes to train the next leaders in genomic science
* Haplotypes are ancestral sections of chromosomes that contain multiple single letter variations (SNPs) and are inherited together in blocks. Rather than searching through millions of SNPs to search for disease genes, a knowledge of haplotypes means that scientists may be able to narrow their search to bundles of 10,000-50,000 letters each.