Dr. Ogbunu works to develop models that explain how infectious diseases evolve, including the emergence of drug-resistant strains.

Dr. Ogbunu earned his undergraduate degree from Howard University. After graduation, he was a Fulbright Scholar in Kenya before returning to school at Yale to complete both a Master’s and Ph.D. in microbiology. His postdoctoral research at the Broad Institute of MIT and Harvard was supported by fellowships from the Broad, Harvard, and the Ford Foundation. He then moved to the University of Vermont, where he was a Henderson Fellow, before joining the faculty as an Assistant Professor.

A new allele (version of a gene) arises in a population as a mutation in a single individual and may or may not be passed on to that individual’s offspring. Over time, that allele can spread through the population until it is present in every individual (fixation) or it can be lost from the population altogether (loss). Each allele has a relative fitness value: the amount that it improves or reduces the individual’s success at reproducing. In simple population genetics models, we assume that the fitness of an allele determines whether it is fixed or lost (eventually). However, in large populations with high mutation rates (e.g. in a microbial population), it is likely that each individual is actually carrying multiple alleles that are at intermediate frequency (i.e. not yet fixed or lost). If these alleles are close together — for example, multiple mutations in the same gene — their likelihood of being fixed in the population will no longer be determined by their individual fitness, but by their combined fitness. It is actually combinations of alleles that are competing to be fixed!

In a recent paper, Dr. Ogbunu and a colleague argue that whether or not a particular combination of alleles gets fixed is determined primarily by the relative fitness advantage of each new mutation added to the combination over its predecessor — not by competition between different combinations. Specifically, this relative fitness advantage determines how quickly the new combination spreads through the population. Using data from malarial parasites treated with anti-malaria drugs (selective pressure), Dr. Ogbunu simulated how long it would take for a particular combination of alleles to arise, given the relative advantage from each step along the way. By comparing different drugs and doses, he was able to predict which would be most effective for delaying drug resistance from arising in the population.