Dhasarathy and Brissette Awarded Department of Defense’s Tick-Borne Disease Research Program grant

Drs. Dhasarathy and Brissette have been awarded a grant through the Department of Defense’s Tick-Borne Disease Research Program.

The bacterial pathogen Borrelia burgdorferi is the causative agent of Lyme disease, the most prevalent tick-borne disease in the United States. This pathogen is capable of long-term infection of humans that can lead to severe arthritis and neurological complications, even in healthy people with intact immune systems. Many patients continue to have debilitating symptoms even after extensive antibiotic treatment, but the reasons behind these symptoms remain unclear. Dr. Dhasarathy and Brissette’s proposal aims to understand underlying mechanisms of persistent symptoms associated with Lyme disease.

In this highly collaborative proposal, they will specifically be examining epigenetic mechanisms involved in Lyme disease. Our genetic makeup, i.e. DNA, can be considered as the hardware, the blueprint for who we are. Epigenetic mechanisms can be considered as the software, that tells the hardware what to do- i.e. determine which genes are turned on or off in different cell types, at distinct times in our lifespan, and in response to environmental stresses that we encounter. Epigenetics is an additional layer of control that sits on top of the genome, (hence the prefix epi-, which means above), and refers to changes in gene activity that do not involve alterations to the genetic code, but still get passed down to at least one successive generation.

Although it is a fundamental mechanism that affects several cell types and diseases, very little research has been done on the role of epigenetics in Lyme disease thus far. The researchers propose to examine  the novel hypothesis that when cells are infected by the Lyme pathogen, they respond by turning on genes involved in inflammatory responses, and that these genes are in turn ‘marked’ or ‘tagged’ by small chemical tags called epigenetic marks that allow cells to ‘remember’ the infection.  While gene activity might return to normal once the infection is removed, the epigenetic marks can persist years after the infection is treated, similar to a bookmark, to “remember” that these inflammatory genes were once turned on. Subsequent inflammatory events unrelated to infection might then lead to a rapid and more robust activation of these epigenetically marked genes, resulting in the debilitating symptoms of RLA.