The Genome Sequencing Center at Washington University School of Medicine in St. Louis has been awarded a $156 million, four-year grant to use the powerful tools of DNA sequencing to unlock the secrets of cancer and other human diseases.
The grant is among the largest awarded to Washington University and one of only three given by the National Human Genome Research Institute (NHGRI) to U.S. sequencing centers. The funds also will be used to improve scientists' understanding of the human genome and to sequence the genomes of non-human primates and microbes.
The three sequencing centers have a proven track record in genome sequencing, which involves spelling out the sequences of letters - A, C, G and T - that make up the genetic codes of all living organisms. The latest funding adds a new dimension to sequencing efforts by focusing on disease genes, particularly those involved in cancer.
"The Human Genome Project gave us the blueprint of the human genome, and now we're ready to comb that genome to find genetic changes that underlie the development of cancer and sustain its growth," says Richard Wilson, Ph.D., director of Washington University's Genome Sequencing Center and a leader in the worldwide scientific collaboration that produced the first human genome sequence in 2000. "We strongly believe that a genome-wide understanding of cancer will ultimately lead to the development of new diagnostic tests and more effective treatments."
The grant underscores the expertise of the Genome Sequencing Center, which has been funded by the NHGRI since 1990 and has been a world leader in the innovative high-speed sequencing of genomes, from primitive bacteria to complex humans. "We are extremely proud to once again play a leading role in genome sequencing, this time with a focus on understanding human health and disease," says Washington University Chancellor Mark Wrighton.
"At a time when funding for basic research is declining in real dollars, the grant is a tremendous shot in the arm for Washington University," says Larry Shapiro, M.D., executive vice chancellor and dean of Washington University School of Medicine. "It shows that the National Institutes of Health has tremendous confidence in our genome sequence center to carry out the next phase of genome sequencing, which is likely to dramatically change the way doctors diagnose and treat disease."
Genetic errors, or mutations, are known to accumulate in normal cells, ushering in a transformation that can eventually lead to cancer. An estimated 300 genes involved in cancer are already known, and a more in-depth search could identify numerous others that determine, among other things, how aggressive a particular tumor is or which drugs might work best to treat it.
The cancer gene sequencing effort is part of The Cancer Genome Atlas, a joint pilot project of the NHGRI and the National Cancer Institute that will initially focus on identifying small changes, like duplications or deletions of genetic material, in three types of cancer: ovarian, lung and glioblastoma, an aggressive brain tumor.
The new research involves sequencing a patient's tumor DNA and comparing it to a normal DNA sample from the same patient to identify changes that may be important to cancer. "We think that cancer at the level of the genome, while complex, can be characterized," says Elaine Mardis, Ph.D., co-director of the Genome Sequencing Center. "Our funding will be directed at a genome-wide understanding of cancer-specific mutations that, for the first time, will enable us to discover and catalogue this information as a first step to finding cancer cures."
The researchers will also sequence the genes involved in other diseases and the entire X chromosome, to identify genes involved in X-linked diseases, such as hemophilia and Fragile X.
As part of the grant, Washington University's Genome Sequencing Center will continue to refine and improve scientists' understanding of the human genome sequence. "Just like any good encyclopedia, you always want to improve and update the information, and that's what we'll be doing for the human genome," Wilson says.
Washington University scientists also will be sequencing the genomes of non-human primates such as the chimpanzee, macaque, orangutan, marmoset and gibbon. Although their genomes closely resemble humans, non-human primates don't get certain diseases common among humans, such as skin cancer or Alzheimer's disease, and the researchers hope clues embedded in the genetic sequence will reveal why.
Additionally, the researchers will sequence the genomes of both infectious bacteria, to determine what makes certain microbes infectious, and of "friendly" bacteria that normally line the intestines and help metabolize food. Another focus is on sequencing pathogens that are a major health problem in developing countries such as the tiny nematode worm that causes river blindness, a disease that affects 16 million worldwide. A better understanding of this organism's genetic code may lead to more effective treatments.
Over the next four years, the centers in the NHGRI program also will mount a major new effort to gather genetic data faster and less expensively than before. "When we first started genome sequencing in 1990, it took eight years and more than $50 million to produce the sequence of the roundworm C. elegans," Wilson says. "Next year, we will be testing new technology that would allow us to sequence the C. elegans genome in two or three days at a cost of $5,000. We are continually working to produce sequences faster, better and less expensively."
The other two sequencing centers funded by the new grant are located at Baylor College of Medicine and the Broad Institute at the Massachusetts Institute of Technology and Harvard University.
Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.