Some people live longer than others. Susceptibility to chronic disease, and many other attributes relevant for aging, also vary from one person to another. These differences are due in part to DNA sequence variants somewhere in our genome, although exactly where is still a mystery in most cases. Mice, worms, flies, and microbes can serve as powerful models for the study of the principles of genetic variation. Research in the Brem lab uses these simple organisms to understand how natural genetic changes impact longevity and health, and how they are shaped by the forces of evolution.
One team of Brem lab researchers is focused on differences across individuals, like strains of mice or isolates of fruit flies. We track down genetic variants that correlate with aging-relevant traits in the population, and we experimentally test their effects. Another team in the Brem lab works on radically different, long-separated species, which cannot mate to form populations. We invent new kinds of experiments to pinpoint the genes responsible for aging and stress resistance traits in these species, many of which have evolved under natural selection.
Why it matters
As we map the DNA sequence variants underlying differences within or between species, we often land on novel genes with no previously known function in aging or health. They lead us to molecules in humans that are of urgent interest in the field as drug targets or diagnostics. And they teach us about when and how evolution has acted to promote stress resistance and longevity in the wild.
Solving the puzzle of why some people age better than others has implications for everyone. Genetic benefits that accrue to one person could be exploited to benefit all.
Rachel Brem, PhD
Dr. Brem is an associate professor and the faculty director of the Bioinformatics Core at the Buck Institute. She earned a PhD in biophysics from University of California, San Francisco, and did postdoctoral research at the Fred Hutchinson Cancer Research Center in Seattle, Washington. Before joining the Buck Institute, she held a faculty position at University of California, Berkeley, where she retains an adjunct appointment.
Dr. Brem is a geneticist and genomicist working at the interface between computation and experiment. She has been the recipient of a Burroughs-Wellcome Career Award, an Ellison New Scholar in Aging Award, and a Glenn Award for Research in Biological Mechanisms of Aging.
Tyler Hilsabeck PhD Candidate, Buck-USC Biology of Aging Program
Taekyu Kang PhD Candidate, Buck-USC Biology of Aging Program
Noah Simon PhD Candidate, Buck-USC Biology of Aging Program
- Hill, R. Z., Hoffman, B., Morita, T., Campos, S. M., Lumpkin, E. A., Brem, R. B., Bautista, D. M. (2018 Mar 21). The signaling lipid sphingosine-1- phosphate regulates mechanical pain. eLife, 7, ii, e33285. DOI: 10.7554/eLife.33285. PubMed PMID: 29561262.
- Coradetti, S. T., Pinel, D., Geiselman, G., Ito, M., Mondo, S., Reilly, M. C., Cheng, Y. F., Bauer, S., Grigoriev, I., Gladden, J. M., Simmons, B. A., Brem, R. B., Arkin, A. P., Skerker, J. M. (2018 Mar 9). Functional genomics of lipid metabolism in the oleaginous yeast Rhodosporidium toruloides. eLife, 7, ii, e32110. DOI: 10.7554/eLife.32110. PubMed PMID: 29521624. Featured article, eLife Digest, March 9, 2018.
- Roop, J. I., Chang, K. C., Brem, R. B. (2016 Feb 18). Polygenic evolution of a sugar specialization tradeoff in yeast. Nature, 530(7590), 336–9. DOI: 10.1038/nature16938. PubMed PMID: 26863195. Featured article, Cell Systems, March 2016.
- Morita, T., McClain, S. P., Batia, L. M., Pellegrino, M., Wilson, S. R., Kienzler, M. A., Lyman, K., Olsen, A. S. B., Wong, J. F., Brem, R. B., Bautista, D. M. (2015 Jul 1). HTR7 is a transducer of serotonergic acute and chronic itch. Neuron, 87(1), 124–38. DOI: 10.1016/j.neuron.2015.05.044. PubMed PMID: 26074006.
- Schraiber, J. G., Mostovoy, Y., Hsu, T. Y., Brem, R. B. (2013). Inferring pathway evolutionary histories from transcriptional profiling data. PLoS Computational Biology, 9(10), e1003255. DOI: 10.1371/journal.pcbi.1003255. PubMed PMID: 24130471.
- Yoon, O. K., Hsu, T. Y., Im, J. H., Brem, R. B. (2012). Genetics and regulatory impact of alternative polyadenylation in human B-lymphoblastoid cells. PLoS Genetics, 8(8), e1002882. DOI: 10.1371/journal.pgen.1002882. PubMed PMID: 22916029.
- Denby, C. M., Im, J. H., Yu, R. C., Pesce, C. G., Brem, R. B. (2012 Mar 6). Negative feedback confers mutational robustness in yeast transcription factor regulation. PNAS, 109(10), 3874–8. DOI: 10.1073/pnas.1116360109. PubMed PMID: 22355134.
Dr. Brem’s Pubmed link