2016 Innovation Competition (Boston, MA)

Block immune evasion by Lyme and other pathogens

Lyme disease occurs worldwide and is one of the fastest growing infectious diseases in the US. Bacteria in the genus Borrelia cause Lyme disease and can cause chronic disability by permanently damaging our central and peripheral nervous system, heart, and joints. Borrelia often appear to be resistant to standard antibiotic treatment. To persist within mammalian hosts, Borrelia must evade the immune system by constantly changing their surface proteins. We aim to block their ability to change the surface proteins, which will allow our immune system to eliminate Borrelia. Recent studies showed that (i) the ability of Borrelia to vary their surface proteins requires DNA recombination mediated by a type of unusual DNA structure called a G-quadruplex, and that (ii) there is a well-tolerated drug developed for cancer treatment that targets a related G-quadruplex. Based on this information, we will identify small molecules that specifically disrupt the Borrelia G-quadruplex by screening molecules related to the existing drugs. We will first conduct a high-throughput phenotypic screen using yeast and also perform virtual screening using the G-quadruplex structure to select candidate drugs for preclinical studies in mice. Those drugs with the highest therapeutic potential will then be used in human clinical trials. Since pathogenesis appears to involve G-quadruplex mediated gene conversion in several infectious agents, targeting the G-quadruplex may be applicable to other diseases.

Yuko Nakajima, Ph.D. email: nakajima@brandeis.edu phone:(617) 902-0352