Hi! My name is Anja Schempf, and I am a rising sophomore at the University of Chicago, where I plan on double majoring in Biology and Molecular Engineering. I have always had an interest in the biological basis of aging, which is what initially drew me to the SRF Summer Scholars Program. I am intrigued with all of the different molecular changes that contribute to the overall process of aging. Aging is not one simple biological process but rather multiple processes occurring in the body which combine to produce the overall effect that we see as aging. I am especially excited to work with the SENS Research Foundation and further research these processes.
The past three summers, I have conducted research with Professor Carola Neumann at the Magee Women’s Research Institute in Pittsburgh. My initial project with Dr. Neumann focused on the enzyme Peroxiredoxin (Prdx1) and its role in the transition of cells to a more mesenchymal (a more invasive and mobile type of cell) phenotype. Prdx1 is an enzyme which works to degrade hydrogen peroxide within the cell to prevent damage to DNA. We believed that lower levels of Prx1would allow cells to develop a more mesenchymal phenotype. To test this hypothesis, I compared knockdown Prdx1 and normal mouse cells. After knocking down the levels of Prdx1 within the cell, I was able to measure the levels of certain proteins that are indicative of the more mesenchymal phenotype. My results showed that lower levels of Prdx1 yielded cells with higher levels of the proteins that were indicative of the mesenchymal, mobile phenotype.
The following year in Professor Neumann’s laboratory, I focused on testing whether the heightened levels of the mesenchymal proteins would actually cause more cell migration. Often, a more mesenchymal phenotype allows for cells to be more mobile, as they are not as attached to the surrounding cells. To test this hypothesis, I measured the amount of migration of normal and knockdown Prdx1 cells. My results showed that not only did the knockdown of Prdx1 increase the levels of proteins that are typical in a more mesenchymal phenotype but also the Prdx1 knockdown cells demonstrated higher levels of migration. This implies that breast cancer cells, which in many cases have mutated to have lower levels of Prdx1, can become more mobile as they develop a more mesenchymal phenotype.
Spermidine’s Effect on Cellular Autophagy and Energy Metabolism in Mice Livers
Autophagy is the process by which cells degrade old and damaged organelles and proteins, allowing the cells to prevent damage inflicted by these impaired components. In humans, autophagy helps to prevent the aging of cells, but levels of autophagy tend to diminish as we age. When autophagy levels are lower, muscle disorders and heart issues can occur [1]. This summer, I am working in Dr. Brian Kennedy’s lab at the Buck Institute for Research on Aging under the supervision of Dr. Chen-Yu Liao. My goal this summer is to discover the effect of spermidine, a natural polyamine (an organic compound with two or more amino groups) which has been shown to increase mouse lifespan, on liver tissue and to understand whether spermidine acts in the same way as another autophagy-inducing chemical, rapamycin. To test this, I will be measuring protein levels in harvested liver tissue from mice that have been treated with spermidine and control mice that have been treated with a water-based salt solution, called PBS.
Figure 1. Spermidine Effect on Lifespan.
Lifelong administering of spermidine through drinking water shows a lengthening of lifespan in both male and female mice. The Y-axis shows the percent of mice still living at each day shown on the X-axis. Eisenberg et al., Nature Medicine, 2016
The main two protein complexes I will be focusing on are mTORC1 (mechanistic target of rapamycin) and mTORC2, which are protein complexes that regulate autophagy and cell regulation as well as cell metabolism. While the drug rapamycin has been shown to reduce autophagy by lowering levels of mTOR1 and therefore elevating autophagy, it is unclear if spermidine acts through the same pathway, despite producing the same effect [2,3] . By testing mTOR levels, I will be able to discover whether spermidine acts using the same pathway as rapamycin. Through the use of Western blots, a method by which protein quantities can be measured based on protein size, I will be able to determine whether spermidine alters the levels of important proteins. These proteins include autophagy proteins such as p-62, Beclin-1, GADPH, and energy metabolism proteins, such as PGC-1a, CPT1A, ATGL, p-HSL, and HSL. Taken together, the status of these proteins will give us a better understanding of the spermidine pathway.
Future Plans:
This coming fall, after returning to Chicago, I will begin working in the lab of Dr. Sarah London, researching the developmental pathways by which the zebra finch acquires the ability to sing. After graduating from the University of Chicago, I hope to attend graduate school, achieve my PhD, and then pursue a career in medical research.
References:
[1] Madeo F, Zimmermann A, Maiuri MC, and Kroemer G. “Essential Role for Autophagy in Life Span Extension.” Journal of Clinical Investigation.125.1 (2015): 85-93. Web.
[2] Lamming DW, Ye L, Sabatani DM, Baur JA. “Rapalogs and mTOR inhibitors as anti-aging therapeutics.” Journal of Clinical Investigation. 3.123 (2013): 980-989.
[3] Ramos FJ, Chen SC, Garelick MG, Dai DF, Liao CY, et al. “Rapamycin Reverses Elevated MTORC1 Signaling in Lamin A/C–Deficient Mice, Rescues Cardiac and Skeletal Muscle Function, and Extends Survival.” Science Translational Medicine. U.S. National Library of Medicine: 1-2. Web.
[4] Eisenberg T, Abdellatif M, Schroeder S, Primessnig U, Stekovic S, et al. “Cardioprotection and Lifespan Extension by the Natural Polyamine Spermidine.” Nature News. Nature Publishing Group, 1-2. Web.
