Math instead of mice: Computational biology, genetics and disease

The wealth of genetic information accumulated in the last decade has enabled
the identification of genetic origins for many birth defects, clinical diseases and syndromes.
While realizing the genetic basis of disease is crucial, a major challenge is to understand
precisely how genetic abnormalities disrupt normal functioning of cells and organs to cause
disease. While one approach for making connections between genes and systems is through
experimentation on animals, our goal is to develop novel theoretical approaches. We have
developed mathematical models of specialized proteins, called ion channels, which control
electrical activity in cells and organs. An example is the heart, where precisely timed
electrical signals determine heart rhythm. In the brain, electrical signals are required
for many normal brain functions, including memory storage and retrieval. Ion channels open
and close with precise timing to allow movement of ions across membranes- a property that
is required for healthy organ function. Genetic mutations in regions of DNA that contain
instructions for building ion channel proteins can lead to abnormal protein structure and
disrupt the opening and closing. The behavior of normal and abnormal channels can be
described using mathematical expressions that are derived from experiments. The questions
that we aim to answer are, “How do these abnormal openings and closings lead to the disease?
What are the effects of abnormal protein functioning on cellular, tissue and organ level
electrical activity?” I will provide ample background on the basics of ion channels, organ
electrical activity, building mathematical models of ion channels, and how we have utilized
this method to uncover mechanisms of abnormal heart and brain rhythms.