Cambridge Rindge and Latin School
Cambridge, MA

Steven Reilly and Elizabeth Brown 
Infectious Disease Initiative

In the past 300,000 years, humans have moved out of Africa into new environments and climates, and have endured challenges due to novel pathogens and dramatic alterations in diet. These powerful evolutionary forces have strongly shaped modern humans, leaving detectable signatures of natural selection in the our genomes. Different populations experienced different evolutionary pressures, leading to genetic variations in humans across the world. Today some of these same variants translate into differences in disease risks across individuals and populations. However, only a few of these adaptive variants have ever been characterized for their impact on human disease and phenotype. The Sabeti lab develops new computation and experimental methods to detect variants under selection and then identify their function.

While in the Sabeti lab, Nico used CRISPR/Cas9 technology to understand genetic variation in West African populations. Specifically, he examined positively selected genetic variants regulating the ERLIN1 gene. This gene is thought to play a role in nonalcoholic fatty liver disease, which shows highly variable rates across different populations. To compliment the computational analysis, he performed functional studies to swap derived and ancestral versions of ERLIN1 variants to test their function. This work will reveal the physiological consequences of ERLIN1 regulatory variants, which is the first step in illuminating their role in human history and how they shape current disease.

“Immersing myself in an environment where I was surrounded by so many brilliant minds was incredibly motivating and I learned more during this time frame than any other. Being around people from all over the world who focus on different disciplines I think was something unique about the Sabeti lab because of the type of research that is conducted, and was an incredible opportunity to meet extremely intelligent individuals who were very open about their work and were always willing to collaborate across disciplines,” said Nico.