At the center of genomics technology development
By Mark Wanner
At the time, many people viewed completing the first human genome sequence in 2003 as a finish line. Instead it turned out to be the starting line for a whole new level of inquiry into human biology, driven by technologies that would have been difficult to even conceptualize less than two decades ago.
Human genomics research proceeded to reveal far more genomic complexity than originally anticipated, and the types of genomic variation found across individuals and populations is still an area of active inquiry. Indeed, the first truly “complete” human genome, which fills in the difficult-to-sequence parts of the genome—roughly eight percent of it—previously left out, was just released as a preprint. And the sequence in isolation, all 3.055 billion base pairs, reveals surprisingly little about many aspects of genome structure and function. Advances in DNA sequencing technology have formed the basis for studying many aspects of genome function, however, including how genes are expressed, how DNA is organized in the nucleus, and how genetic variation affects both.
To push the capabilities still further, the National Human Genome Research Institute (NHGRI) launched a Genome Technology program in 2004 to support the development and early dissemination of innovative new genomic methods, technologies and instruments. Since then, the funded programs have grown to encompass many new aspects of genomic analysis including nanopore sequencing, epigenetic analysis, and analysis of genome function in individual cells. And, just recently, NHGRI turned to The Jackson Laboratory (JAX) to help coordinate this extensive effort.
“There is a lot of exciting genome technology work being done by groups around the country,” says JAX Professor , Ph.D., who is the principal investigator for the newly formed Technology Development Coordinating Center (TDCC). “Our role is to support these programs by facilitating collaboration, enhancing the use of common standards for evaluating advances, and ensuring that the results from the program are widely available to the research community. We expect that the TDCC will increase the effectiveness of the program as a whole.”
The NHGRI was established in 1989 as the National Center for Human Genome Research. Originally formed to lead the National Institutes of Health’s (NIH) participation in the Human Genome Project, which launched the following year, it became an official research institute within the NIH in 1997. As its revised name implies, the NHGRI has supported human genomics research and the effort to translate research findings to medical progress since.
Genomic research technologies have already advanced with dizzying speed. Sequencing whole genomes is now routine, analysis pipelines have improved, and three-dimensional genomic organization and structure can be determined. Researchers are also able to investigate genomic attributes that alter function but not the sequence, such as the 3D structure of the genome and epigenetic marks (structural and chemical modifications to DNA that frequently help regulate gene expression). Nonetheless, much remains to be learned about how cells “read” the genome to produce the characteristic functions of each cell type.
Through the Genome Technology program, the NHGRI began by funding scientists in academic centers, as well as researchers in companies through small-business grants. The goal was to catalyze the development of new DNA and RNA sequencing technologies and improve methods for evaluating gene regulation, nuclear organization, and genomic features, including at the single-cell level. In 2021, the program is expanding to add synthetic nucleic acid technology development projects to its portfolio, funding projects to inexpensively and accurately synthesize specified sequences and constructs at genomic scales. The NHGRI formed the TDCC to provide a hub for these researchers to share insights and find opportunities to work together where their research priorities align.
The TDCC’s role encompasses several facets. It will promote collaboration among the grantees and lead efforts to develop and promote standards for the technologies developed within the program. The standards will provide benchmarks to help the genomics research community as a whole understand the advantages of new methods. The center will develop outreach approaches and educational materials to engage the community of genomic researchers and provide key information resources. It will also oversee an Opportunity Funds program to support new, innovative pilot projects that might be too early-stage for a traditional research grants, but could catalyze important improvements and advances for the field.
JAX-Genomic Medicine in Farmington, Conn., was established in 2012 with a focus on human genomics, complementing JAX’s long history of mammalian genetics expertise.
“JAX has a long history of collecting, curating and sharing information resources with researchers, and that is a priority for the NHGRI,” says Adams. “Also, our education and courses and conferences programs will play a significant role in our outreach efforts.” The outreach efforts of the TDCC will be led by Brent Berwin, Ph.D., JAX’s Director of Courses and Workshops.
The past decade has been marked by significant leaps in technical capabilities and the translation of genomic discoveries into the clinic. The Genome Technologies program and the TDCC promise to pave the way for even more exciting discoveries and technology advances in the years ahead, always with the goal to improve medicine through better understanding of our own biology.