Eminent Toxicologist Lecture Notes

Dr. Cheryl Lyn Walker “Environmental Epigenomics: The Developmental Origins of Health and Disease”

Learning Objectives:

  1. Exposure to chemicals early in life while our tissues are undergoing development can alter normal physiological responses in adulthood.
  2. This “Developmental Programming” can determine risk of diseases such as heart disease, obesity, and cancerinadulthood.
  3. This suggests that adult risk of diseases, such as cancer, may be determined by environmental exposures that occurred in early life, possibly decades, before disease presentation.

Recommended prerequisite topics

  • Central Dogma (how DNA codes for protein)
  • Molecular biology techniques
  • Basic epigenetics

Study questions

  1. What is the potential human health impact of developmental exposure to endocrine disruptors?
  2. What is an example of a toxicant that early life exposure to can cause disease later in life?
  3. Who was the first to formulate the fetal origin of adult disease hypothesis? What stressor and physiological endpoints did his research link?
  4. In your own words, use a computer analogy to explain the interaction of the genome and epigenome.
  5. Give at least one example of a writer, eraser and reader of the epigenome.
  6. Why is diethylstilbesterol (DES) an example of an endocrine disrupter? List some other examples of EDCs.
  7. In your own words, explain the concept of gene-environment interactions.
  8. Compare and contrast the following three molecular techniques with respect to what biological endpoints they are useful for measuring: Western blot, RNASeq, ChipSeq.
  9. What sorts of interventions may ultimately prove useful for resetting epigenetic reprogramming?

Note to undergraduate educators: if your time is limited or class a more basic level you may want to use the first 22 minutes and then skip to slide 50 for conclusion. The slides 27 – 49 describe the experimental evidence for EDC epigenetic remodeling in reproductive tract cancers and may be beyond the scope of an undergraduate class if the students don’t have a strong molecular biology background.

Application of this Lecture to Vision and Change Core Concepts and Competencies.

Core Concepts
Evolution / Comparisons are made between how gene expression is controlled with respect to the genome and epigenome.
Structure and Function / Lecture describes reprogramming of physiological set points including examples of diabetes, growth retardation/hypertension and obesity.
Information flow, exchange, and storage / The historical perspective of our understanding of how our early life environment alters congenital abnormalities, physiological set points and molecular reprogramming is provided.
Gene x environment interaction discussed.
Pathways and transformations of energy and matter
Systems
Core Competencies
Ability to apply the process of science. / Emphasis early in the lecture on the history of the field provides excellent insight into the process of science.
Ability to use quantitative reasoning / The rationale for formulating hypotheses, experimental test design, data analyses and conclusions are provided for three EDCs that cause latent reproductive cancers following developmental exposure.
Ability to use modeling and simulation
Ability to tap into the interdisciplinary nature of science / The fetal basis of adult disease requires interdisciplinary knowledge between the fields of developmental biology, toxicology and pathology.
Ability to communicate and collaborate with other disciplines / This lecture highlights the overlap between toxicology and cancer biology.
Ability to understand the relationship of science and society / Better understanding of the mechanisms of developmental reprogramming will potentially allow for interventions later in life (dietary, lifestyle, pharmacologic) to off-set disease progression. Also better understanding of the fetal basis of adult disease will allow parents to better protect their offspring during critical developmental stages.

Vision and Change Core Concepts.

  1. Evolution. The diversity of life evolved over time by processes of mutation, selection, and genetic change.
  2. Structure and Function. Basic units of structure define the function of all living things.
  3. Information flow, exchange, and storage. The growth and behavior of organisms are activated through the expression of genetic information in context.
  4. Pathways and transformations of energy and matter. Biological systems grow and change by processes based upon chemical transformation pathways and are governed by the laws of thermodynamics.
  5. Systems. Living systems are interconnected and interacting.

Core Competencies and Disciplinary Practice.

  1. Ability to apply the process of science. Biology is evidence based and grounded in the formal practices of observation, experimentation, and hypothesis testing.
  2. Ability to use quantitative reasoning. Biology relies on applications of quantitative analysis and mathematical reasoning.
  3. Ability to use modeling and simulation. Biology focuses on the study of complex systems.
  4. Ability to tap into the interdisciplinary nature of science. Biology is an interdisciplinary science.
  5. Ability to communicate and collaborate with other disciplines. Biology is a collaborative scientific discipline.
  6. Ability to understand the relationship of science and society. Biology is conducted in a societal context.