Robin Stanley, Ph.D., and Clarice Weinberg, Ph.D., are the recipients of the 2021 NIEHS Scientific Director’s Award of Excellence. Scientists at the institute each receive $ 100,000 to advance their research efforts , which have been recognized as outstanding by the Council of Scientific Advisors of the NIEHS Intramural Research Division.
Stanley, a Stadtman researcher who heads the institute’s nuclear integrity group, won the award for his research into the enzymes involved in RNA processing. She said she plans to use her reward money to purchase the necessary equipment and perform RNA processing tests.
Weinberg, a senior researcher at the NIEHS Biostatistics and Computational Biology Branch, has been recognized for her research on epistasis, which is the interaction between genetic variants that could cause a specific trait or disease. His prize will allow him to sequence the genomes of 400 families affected by breast cancer as part of the Study of two sisters(https://sisterstudy.niehs.nih.gov/english/twosisterstudy.htm). The study examines women who develop breast cancer when they are under 50 and what genetic and environmental factors may be involved. Weinberg has already won the Excellence Award in 2017 (see box).
RNA disruption and disease
Stanley said her job is the business of basic science – in this case, investigating how the factors involved in RNA processing coordinate the production of ribosomes, which she describes as large machines in the cells that make proteins.
The assembly of ribosomes takes place in the nucleolus, the heart of the cell. The nucleolus is linked to ribosomal RNA. Our bodies cannot live without the production of ribosomes. Heat shock, hypoxia, and UV damage, among other environmental factors, can affect the way our cells make ribosomes. And under stress, the nucleolus can undergo a dynamic change.
“Many assembly factors can move in and out of the nucleolus,” Stanley observed. “Are they leaving the nucleolus because they need to do something else, are they leaving to protect it, or are they leaving to stop a track?” We want to understand the protein shuttle to determine what happens when the cell is under stress.
Last year, Stanley’s lab switched from studying ribosomal RNA processing to treatment of viral RNA, especially in SARS-CoV-2, which causes COVID-19.
“Regarding the SARS-CoV-2 RNA processing factors, we want to better understand how they work so that we can design inhibitors to turn them off,” Stanley added.
âRobin is an outstanding structural biologist who has done incredible work on ribosome assembly proteins,â said Darryl Zeldin, MD, Scientific Director of NIEHS. âI am impressed with how she has shifted gears to tackle important research questions related to COVID-19. “
Genetic variants and environmental exposures
Weinberg’s research with a student and colleagues examines the joint effects of genetic variants in families with early-onset conditions such as cleft lip and cleft palate, and the interaction of environmental exposures.
âThe reason it’s so hard to find epistatic effects is that there are so many combinations that you have to look at,â Weinberg said. âIt can be overwhelming to sort everything. “
By exploring data involving many combinations of genetic variants, his group will probe epistatic and de novo mutations – those seen in the offspring but not in the parents – in the Two Sister study. She hopes to sequence the genomes of more than 400 participating families – women with breast cancer, their cancer-free sisters and their parents.
âMuch of what remains to be learned involves interactions of genetic variants and environmental exposures,â Weinberg said. âSome people are probably genetically vulnerable, for whatever reason, to environmental effects. What factors make others invulnerable? “
âClare did a terrific job with the Two Sister Study, examining the genetic and environmental factors associated with breast cancer,â Zeldin said. “She is an icon in the biostatistics community.”
Quote: Pillon MC, Frazier MN, Dillard LB, Williams JG, Kocaman S, Krahn JM, Perera L, Hayne CK, Gordon J, Stewart ZD, Sobhany M, Deterding LJ, Hsu AL, Dandey VP, Borgnia MJ, Stanley RE. 2021. The cryo-EM structures of endoribonuclease SARS-CoV-2 Nsp15 reveal insight into the specificity and dynamics of the nuclease. Nat Common 12 (1): 636.
(Kelley Christensen is a writer and contract writer for the NIEHS Office of Communications and Public Liaison.)