The National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, selected Yarui Diao and Craig Lowe, two Genomic and Computational Biology (GCB) faculty, to receive 2020 Genomic Innovator Awards. NHGRI honored a total of 12 early career investigators in genomics. Each awardee will receive five years of funding.
The Genomic Innovator Award supports innovative work by genomics investigators who are in the early stages of their careers and are part of consortia or other team-science efforts. This award allows researchers the flexibility to pursue innovative research directions in genomics.
Analyze the molecular composition associated with non-coding DNA and RNA sequences
Yarui Diao is focused on gaining a better understanding of the function and regulation of the non-coding genome in health and disease. The Diao lab will develop a CRISPR-based BioID method that uses a functional multi-omics approach to characterize the molecular composition associated with non-coding regulatory DNA and RNA. This will allow them to identify the “molecular handle” that can be engineered to create a proof-of-principle study to reverse the aging phenotype by manipulating the activity of the non-coding regulatory genomic sequence.
“In aging and in many disease including cancer,” Diao said, “there’s dysregulation of non-coding regulatory elements in the genome, but we don’t know the mechanisms that control it.”
Once they develop their CRISPR-based BioID tool, as proof-of-principle, they will apply it to compare young versus aged mice and identify the molecules and proteins responsible for aging-associated genomic activation in skeletal muscle, which may eventually lead to muscular disorder.
“Hopefully by targeting these molecules, we can manipulate genome activity at will, and expand the ‘druggable genome’ for genomic medicine.”
Characterize the fastest evolving regions in the human genome
Craig Lowe will use his award to work on developing a high throughput assay to quantify the gene regulatory potential of DNA sequences in developing tissue. Lowe wants to better understanding the genetic basis of uniquely human traits to help answer why humans may be uniquely susceptible to certain types of disorders and diseases. Understanding the genetic and mechanistic phenotypic differences in development may help come up with paths for improved treatment options.
For example, while humans typically consider bipedalism advantageous, it may also make us more susceptible to knee and back injuries and pain. Typically, these injuries happen to adults, but that doesn’t mean that the root cause of the pain occurred at the time of injury or even as adults. It’s probable that those first molecular events happened during childhood.
“Bones, for example, may have some regulatory elements that change the way they are shaped,” Lowe said. “Down the road, that could create hip problems, but by the time it has created hip problems, you can’t analyze the cells or the gene regulatory elements to see what has happened.”
Lowe, using data from genome-wide associated studies (GWAS), will look for sections of human DNA that seem important. He will then take that bit of human DNA, put it in a plasmid and put it in a model organism to see what that bit of human DNA does earlier in life.
In addition to studying muscular and skeletal tissue, they can use this same approach to look at other tissue, like the brain, and gain a better understanding of other uniquely human traits and disorders.