Grant: Project Grant

The impact of fungal pathogens on human health is devastating. They infect billions of people around the globe, and kill more than 1.5 million each year. The most vulnerable are people with reduced immune function, such as those with HIV or those undergoing immune suppressing treatments for cancer or organ transplants. One of the leading fungal pathogens of humans is Candida albicans. It kills ~40% of people suffering from bloodstream infections. Treating these infections is extremely difficult, as fungi are closely related to humans and there are very few drugs that kill the fungus but not the host. With the emergence of drug resistance, it is now critical to develop new therapeutic strategies. To address this important clinical need, it is critical to uncover the genes and genetic networks that are required for the pathogen to survive and cause disease. We are one of the first academic labs to obtain a powerful resource that will allow us to test the function of almost every gene in the C. albicans genome. Through collaboration with a pharmaceutical company, we now have access to the largest library of C. albicans mutants, which enables genetic depletion of ~40% of genes in the genome. We will use sophisticated computational approaches to predict essential genes, and will expand this resource to cover them all. This resource provides an unprecedented opportunity to identify which genes are essential to the pathogen, and to determine their molecular function. We will use this platform to characterize the impact of reducing the dosage of each gene on growth, cellular physiology, and traits associated with the capacity to cause disease. We will perform state-of-the-art screens to identify new molecules that target essential genes, and will evaluate their therapeutic potential. This research will reveal new approaches to cripple the pathogen, and enable development of novel therapeutic strategies to improve clinical outcome for millions of people.