Grant: Project Grant

Fungi are significant and increasing mediators of pathogenesis; causing serious challenges medically and economically. Candida albicans is the most prevalent cause of fungal infections in people, and can cause life-threatening systemic infections if our immune defenses are compromised. A battery of fitness attributes promote the pathogenicity and drug resistance of this fungus, most of which arise by rapid generation of genetic diversity within a population in response to stressful growth conditions, such as exposure to antifungal drugs, as a means of adaptation. Research has shown that aneuploidy (an abnormal number of chromosomes) accounts for much of this diversity, and that this condition often arises from changes in components of the chromosome segregation machinery. Our findings indicate that some of these changes could be induced or enabled by kinesin motor proteins that regulate the structure of the cell's chromosome segregation apparatus - 'the mitotic spindle'. By addressing central questions about how kinesins control the assembly and function of the mitotic spindle, and how they integrate spindle function with cell division, we will provide insight into an important mutational process generating chromosome aberrations in fungal genomes that lead to drug resistance.