Posted on by Dr. Francis Collins
Step inside the lab of Dana Dolinoy at the University of Michigan, Ann Arbor, and you’re sure to hear conversations that include the rather strange word “agouti” (uh-goo-tee). In this context, it’s a name given to a strain of laboratory mice that arose decades ago from a random mutation in the Agouti gene, which is normally expressed only transiently in hair follicles. The mutation causes the gene to be turned on, or expressed, continuously in all cell types, producing mice that are yellow, obese, and unusually prone to developing diabetes and cancer. As it turns out, these mutant mice and the gene they have pointed to are more valuable than ever today because they offer Dolinoy and other researchers an excellent model for studying the rapidly emerging field of epigenomics.
The genome of the mouse, just as for the human, is the complete DNA instruction book; it contains the coding information for building the proteins that carry out a variety of functions in a cell. But modifications to the DNA determine its function, and these are collectively referred to as the epigenome. The epigenome is made up of chemical tags and proteins that can attach to the DNA and direct such actions as turning genes on or off, thereby controlling the production of proteins in particular cells. These tags have different patterns in each cell type, helping to explain, for example, why a kidney and a skin cell can behave so differently when they share the same DNA.
Some types of genes, including Agouti, are particularly vulnerable to epigenomic effects. In fact, Dolinoy has discovered that exposing normal, wild-type (brown) mice to certain chemicals and dietary factors during pregnancy can switch on the Agouti gene in their developing offspring, turning their coats yellow and their health poor. Dolinoy says these experiments raise much larger questions: If researchers discover populations of humans that have been exposed to lifestyle or environmental factors that modify their epigenomes in ways that may possibly contribute to risk for certain diseases, can the modification be passed on to their children and grandchildren (referred to as transgenerational epigenetic inheritance, a controversial topic)? If so, how can we develop the high-precision tools needed to better understand and perhaps even reduce such risks? The University of Michigan researcher received a 2015 NIH Director’s Transformative Research Award to undertake that challenge.
Posted on by Dr. Francis Collins
For questions about why people often think, act, and perceive the world so differently, the brain is clearly an obvious place to look for answers. However, because the human brain is packed with tens of billions of neurons, which together make trillions of connections, knowing exactly where and how to look remains profoundly challenging.
Undaunted by these complexities, researchers involved in the NIH-funded Human Connectome Project (HCP) have been making progress, as shown by some intriguing recent discoveries. In a study published in Nature Neuroscience , an HCP team found that the brains of individuals with “positive” traits—such as strong cognitive skills and a healthy sense of well-being—show stronger connectivity in certain areas of the brain than do those with more “negative” traits—such as tendencies toward anger, rule-breaking, and substance use. While these findings are preliminary, they suggest it may be possible one day to understand, and perhaps even modify, the connections within the brain that are associated with human behavior in all its diversity.