Molecular and Computational Biology on the Cutting Edge
USC College faculty garner high marks and grants from the National Institutes of Health.
Faculty in USC College’s Department of Biological Sciences earned exceptionally high priority scores from the National Institutes of Health (NIH) during the past year, which will translate to generous funding for their diverse, cutting-edge research projects.
An unprecedented five professors in molecular and computational biology (MCB) will receive grants from the NIH: Myron Goodman, Norman Arnheim, Sergey Nuzhdin, Susan Forsburg and Frank Alber. All will be funded by NIH including several who have received specific dollar amounts and project timeframes for their proposals. An additional two professors are expected to receive notification of funding by NIH in late spring.
According to the NIH’s Web site, each scored grant application is assigned a single, global priority score that reflects the proposed project’s scientific and technical merit based on consideration of the five review criteria: significance, approach, innovation, investigator and environment.
The proposals were enthusiastically received by NIH with four of the five receiving percentile rankings ranging from two to seven percent.
The proposal submitted by Myron Goodman, professor of biological sciences and chemistry, resulted in a more than $2 million award for a biochemical study on error correction in DNA synthesis that focuses on the enzymes called polymerases.
Goodman explained that DNA polymerases replicate parental DNA so that when a cell divides, a duplicate and accurate copy of an organism’s genome passes on to the daughter cell. However, specialized DNA polymerases exist that are deliberately inaccurate, enabling these “sloppier copiers” to replicate damaged DNA and generate mutations that can enhance a cell’s fitness in times of stress.
“It would seem prudent to regulate the access of such low fidelity polymerases to DNA to avoid generating a mutational catastrophe,” Goodman said.
The discovery in Goodman’s laboratory of an error-prone DNA polymerase in the bacteria Escherichia coli that can be activated, deactivated and reactivated offers a new way to regulate mutagenesis. This type of on-off-on switch has never been seen for any high or low fidelity DNA polymerase.
Susan Forsburg, professor of biological sciences, will investigate how cells in meiosis respond to DNA damage. Forsburg noted that a substantial fraction of birth defects result from chromosomal defects in meiosis, the process that produces eggs and sperm. Her team of researchers will use genetics and cell biology in simple yeast to study how chromosomes in meiosis are protected from DNA damage that may contribute to meiotic defects.
“Our goal is to identify conserved proteins that protect meiotic cells from defects that could contribute to birth defects,” Forsburg said.
Norman Arnheim, Distinguished Professor, Ester Dornsife Chair in Biological Sciences, and professor of biological sciences and biochemistry, and co-investigator Assistant Research Professor of Biological Sciences Peter Calabrese were awarded a more than $2 million grant to examine specific inherited human disease mutations causing thyroid cancer that arise with increasing frequency as men age.
“We found that cells of the testis that experience such a mutation form clusters that increase in size with the man’s age and produce sperm that carry an ever-increasing proportion of the disease mutation,” Arnheim said.
Arnheim’s current project aims to identify additional genetic diseases that have this property. The research duo are also interested in elucidating the molecular mechanisms that explain how normal testis cells acquire this unusual property when they become mutated.
Frank Alber, assistant professor of biological sciences, and his team of researchers will develop methods for studying how protein complexes distribute in the cell at different points in time.
According to Alber, knowing the spatial and temporal organization of the proteome at a cellular level is essential to understanding how these macromolecules perform their biological functions.
“The proposed methods will significantly contribute to knowledge in this area of research and will have strong relevance to public health,” Alber said. He noted that proteins need to appear in exact places at exact times to accomplish their roles—any discrepancies may lead to diseases.
Sergey Nuzhdin, a population genomicist and professor of biological sciences, underscores that MCB’s success correlates to a high level of collaboration among faculty, citing his work with developmental biologist and co-investigator Michelle Arbeitman, Gabilan Assistant Professor of Biological Sciences. “Without the technology she generated, there was zero success probability that I could have generated the questions for my proposed study,” Nuzhdin said.
Nuzhdin, who was funded for $1.6 million, will investigate how genetic differences cause alterations in neural functions that ultimately cause variability in social learning. “Although common across taxa, social learning requires the integration of associative learning, memory and social behavior (LMS), and these vary considerably among individuals within a species,” Nuzhdin said.
To address this question, genes and neural circuits must be identified that play a role in LMS. Nuzhdin’s team will analyze the molecular-genetic basis that underlies individual differences in LMS in the fruit fly Drosophila melanogaster. Flies, social animals that aggregate in large groups, are used extensively as a model to study the genetic basis of development, behavior and learning.
“We believe our inferences will illuminate through individual genotype synthesis of genetic, molecular and behavioral information, the range of LMS variation maintained in natural populations of flies,” Nuzhdin said. “This insight will ultimately help decipher aspects of the population genetics of social learning in humans and other social organisms."
To learn more about molecular and computational biology in the College, visit college.usc.edu/bisc/molecular/home
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