Manuel Larach will determine the genetic requirements for effects of Bisphenol-A (BPA) on germ cell chromatin de-silencing in the nematode C. elegans. Previous research in the Allard lab found that environmental chemicals like BPA can cause reproductive, epigenetic, and transgenerational effects in C. elegans. Larach will use RNAi to silence genes involved in epigenetic regulation in C. elegans germlines. Worms will then be exposed to BPA to determine if silencing those genes impacts BPA's epigenetic effects. Analyzing the worms can offer insight into genetic requirements for environmentally induced germ cell toxicity through epigenetic pathways.

1. Manuel Larach
SMC/UCLA SRI Program
Determining the genetic requirements for Bisphenol-A effects on germ cell
chromatin de-silencing.
Thousands of chemicals are released into the environment without a clear
understanding of the effects they generate on our health. Many health problems can be
controlled or prevented by knowing the effects chemicals bring about on biological
processes. Research studies suggest that environmental exposures, including
chemotherapeutic agents, alcohol, plastics, and pesticides may cause diverse diseases
(Hales et al. 2005; Harkonen 2005; Hunt et al. 2003). Chemicals released into the
environment, one example being pesticides like Vinclozolin, have adverse effects on
human health and can cause disease, including cancer (Sharpe., Irvine. 2004). In other
cases, adverse health effects caused by chemicals can be passed from one generation
to another through a changed or altered germline. A key example is the exposure
studies to the synthetic estrogen Di-Ethyl-Stilbestrol (DES). DES is a developmental
stage-specific non-genotoxic carcinogen that was used in the past to prevent
miscarriages in pregnant women. Several studies many years later found effects
ranging from genital malformations to sterility and cancer in children and great
grandchildren of women initially exposed, showing us that effects can not only be
delayed but also passed down for multiple generations. Currently, we are unable to
efficiently and comprehensively assay the multitude of chemicals in the environment for
their effect on germline function and reproductive health (Allard et al. 2013). Our priority
is to find quick and alternative methods to ethically asses these thousands of chemicals
that may be causing reproductive epigenetic effects that are then being passed down
for multiple generations.
The Allard lab studies reproductive and developmental effects caused by environmental
exposures using the genetic model organism Caenorhabditis elegans (C. elegans).
Using this model, they have obtained preliminary data showing that environmental
chemicals, like BPA, can cause reproductive, epigenetic, and transgenerational effects.
Following up these findings, my research project will focus on determining the genetic
requirements for environmental effects on germ cell chromatin disruption. RNAi will be
utilized to silence genes that are important in epigenetic regulation in the C. elegan
worm germline. After silencing these genes, the worms will be exposed to BPA to
determine if they are indeed important in the pathway that causes epigenetic effects
from chemical exposure. Liquid exposure will be implemented to expose the worms to
the chemical compound of interest. Worms will be exposed to BPA in 1.5ml tubes to a
control (0.1%DMSO) and 100uM [C] BPA after RNAi treatment then analyzed for
epigenetic disruption. Results will offer a more comprehensive view of these genetic
requirements and allow us to further characterize the role of epigenetic pathways in
environmentally induced germ cell toxicity.