Michelle Mantilla
Michelle Mantilla, a sophomore biochemistry major at Wellesley College, characterized SLC16A11 protein expression and stability under different cell culture environments.
Complications related to type 2 diabetes (T2D) are the leading cause of death in Mexico.
The Broad has allowed me to explore the delicate line that lies between the known and the unknown. The collaborative and welcoming environment that the Broad fosters in research encouraged me to grow more comfortable with this chase of the unknown and cultivated my passion for research.Although environmental conditions, such as diet and exercise, lead to the development of T2D, there are also strong underlying genetic factors that contribute to risk of the condition. A genome wide association study recently identified a haplotype of genetic variants at the SLC16A11 locus, common amongst individuals of Mexican and Latin American descent, that increases the risk of developing T2D. The T2D risk variants decrease the expression and function of SLC16A11, a proton-coupled monocarboxylate transporter that is predicted to play a key role in hepatic lipid metabolism. Therefore, individuals with T2D may benefit from the development of therapeutic approaches that increase hepatic SLC16A11 levels. SLC16A11 mRNA expression is not homogeneous amongst liver cells, with greater levels observed within pericentral (PC) hepatocytes surrounding the liver’s central vein. This increase in mRNA expression can be modeled in vitro by changing cell culture conditions to reflect the pericentral environment (lower oxygen tension and less nutrient rich) and may lead to increased SLC16A11 protein levels. SLC16A11 protein has a short half-life; therefore, we are testing the effects of these PC-like conditions on SLC16A11 protein stability by western blotting at different times after treatment with cycloheximide. One way in which stability may be affected is through interactions with basigin, a protein that promotes cell-surface localization, and other SLC16A11 subunits. By understanding the mechanisms that increase SLC16A11 levels, this work will contribute to the effort to develop a treatment for T2D.
Project: Amelioration of SLC16A11 expression and stability by altering cell culture environment
Mentor: Alina Ainbinder, Diabetes Research Group