Innovative Efforts Target Epigenetics, Molecular ImagingHarvard Medical School Harvard, Johns Hopkins Named Centers of Excellence in Genomic Science The National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), today announced it has awarded two new grants to establish Centers of Excellence in Genomic Science (CEGS) at Harvard Medical School in Boston and the Johns Hopkins University School of Medicine in Baltimore.  The Harvard and Johns Hopkins centers, like the seven other centers funded through NHGRI's CEGS program since 2001, will assemble interdisciplinary teams of scientists to make critical advances in genome science. The Harvard center will strive to develop new technologies for molecular and genomic imaging, while the Johns Hopkins center will be devoted to advancing the emerging field of epigenetics. "These centers represent key building blocks in our effort to lay the groundwork for new genomic approaches to the study of human biology and disease," said NHGRI Director Francis S. Collins, MD, PhD. "By pulling together researchers from many different disciplines, we believe that we will foster extraordinary collaborations that will advance not only the field of genomics, but biomedical research as a whole." At the first new center, a team led by Harvard's George Church, PhD, will address the biomedical research community's need for better and more cost-effective technologies for imaging biological systems at the level of DNA molecules (genomes) and RNA molecules (transcriptomes). The center will receive $2 million annually in CEGS funding for five years. Specifically, the Harvard center plans to further develop polymerase colony sequencing technologies for studying sequence variation in biological systems. In this highly parallel method of nucleic acid analysis, a sample of DNA is disbursed as many short fragments in a polyacrylamide gel affixed to a microscope slide. Researchers then add an enzyme called polymerase that prompts each DNA fragment to copy itself repeatedly and form tiny colonies, called polonies. Next, the polonies are exposed sequentially to free DNA bases tagged with fluorescent markers, and the incorporation of those bases into the polonies is monitored with a scanning machine. This produces a read-out of the DNA sequence from each polony. A computer program then puts the DNA sequences of the individual polonies into an order that reflects the complete sequence of the original DNA sample. The ordering process is accomplished by aligning the sequences of the individual polonies with a reference DNA sequence, such as the sequence produced by the Human Genome Project. In addition to its application in DNA sequencing, polony technology can be used to study the transcriptome (RNA content) of cells and to determine differences in genome sequence between different individuals (genotypes and haplotypes). The technology developed by Church's team currently can read a slide with 10 million polonies in about 20 minutes, making it one of the swiftest DNA sequencing methods now available and also one with potential for leading to quicker, more cost-effective ways of sequencing individual genomes for use in research or clinical settings. Sequencing a mammalian-sized genome currently costs at least $10 million, but NHGRI's aim is to dramatically reduce that cost to $1,000 over the next 10 years. "In order to reach that ambitious goal, we will need to develop a completely integrated system that requires very small volumes of reagents and that utilizes very inexpensive instruments. Ideally, the system would cost no more than a high-quality, desktop computer," said Dr. Church. The ability to cost effectively sequence each person's genome could signal the end of "one size fits all" approach to medicine, and give rise to more individualized strategies for diagnosing, treating, and preventing disease. Such information also could enable doctors to tailor prescribing practices to each person's unique genetic profile. Along with its tremendous promise, such technology raises a number of ethical, legal and social questions. The Harvard center plans to examine issues related to moving such technologies into the clinic, with emphasis on the challenges that personal genome screening may pose to concepts of anonymity, as part of its CEGS grant. In addition to advancing technologies that may revolutionize clinical research and the practice of medicine, the Harvard Center will strive to develop new tools for studying basic biological processes, including differentiation of neural cells, alternative splicing of RNA in mammalian cells and asymmetric cell division in mammalian stem cells. Under the second CEGS grant, which is funded equally by NHGRI and the National Institute of Mental Health, Andrew Feinberg, MD, and his colleagues will establish the Center for Epigenetics of Common Human Disease at Johns Hopkins. It is believed to be the first university-based research center devoted to studying epigenetics, which is the study of heritable changes in gene function that occur without a change in DNA sequence. The center will receive $1 million annually in CEGS funding for five years. Epigenetic modifications, or marks, involve the addition of certain molecules, such as methyl groups, to the backbone of the DNA molecule. Such modifications change the way in which genes interact with the transcriptional machinery that turns genes on or off, thereby spurring or preventing the production of the proteins that those genes encode. Also, for certain genes, the addition of methyl groups serves to distinguish between the gene copy inherited from the father and the one inherited from the mother – a situation referred to as imprinting. For some genes, only the paternally imprinted copy is activated to produce proteins and for others, only the maternally imprinted copy is used. Paternally-expressed imprinted genes generally code for proteins that promote cell growth, while maternally-expressed imprinted genes play a role in suppressing cell growth. Consequently, the gain or loss of such epigenetic marks can lead to cancer and other diseases by upsetting the cell's normal growth cycle. There is also evidence in mice that some imprinted genes may play a role in behavior. The interdisciplinary team led by Dr. Feinberg, who has pioneered the study of epigenetics in cancer, will develop tools to create comprehensive, genome-wide information about epigenetics and then apply that information to the study of autism and bipolar disorder. In addition, the epigenetic information and technologies will be made available to researchers investigating other diseases. "Epigenetics doesn't underlie all human disease. But it may be as important in certain conditions as the DNA sequence is in other cases," Dr. Feinberg said. "We definitely need to develop the technology to figure out when and where epigenetic changes do influence health and disease." Among the first items on the researchers' to-do list is the development of technologies to speed identification of epigenetic marks and their locations across the entire human genome – to essentially create a map of the "epigenome." Next, in collaboration with researchers from Pennsylvania State University in University Park, Pa.; Epigenomics, Inc., of Berlin; and the Icelandic Heart Foundation, Feinberg's team will use the new technologies to examine the epigenomes of families involved in ongoing studies of autism, biopolar disorder and other common disorders. Also participating in the center's work are two NIH researchers: Eric Green, MD, PhD, director of NHGRI's Division of Intramural Research, and Tamara Harris, MD, MS, chief of the Geriatric Epidemiology Section at the National Institute on Aging. As part of the new center, Feinberg and his colleagues will also implement an action plan to encourage under-represented minorities to pursue education and careers in the field of genomics. The plan will offer select Baltimore-area students the chance to conduct genetic research during their summer breaks and will also work to add a genomics component to the summer classes offered by the Center for Talented Youth, a Johns Hopkins program with sites across the nation. Likewise, the Harvard center will offer opportunities for genomics-related research and training to college and post-college students from under-represented communities. Previous recipients of CEGS grants are:
NHGRI is one of 27 institutes and centers at NIH, an agency of the Department of Health and Human Services. The NHGRI Division of Extramural Research supports grants for research and for training and career development at sites nationwide. Information about NHGRI can be found at www.genome.gov.
For more information, or to contact Harvard Medical School, see their website at: www.hms.harvard.edu |
 |
Email Article To A Friend |  |
Link to us! |
