The Chemical Biology of Naturally Occurring Redox-Active Small Molecules

Harvard Medical School, Boston MA

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Abstract

DESCRIPTION (provided by applicant): An overarching goal of chemical biology is to find small molecules to modulate biological processes of interest. This proposal focuses on applying redox-active small molecules, which are generally unexploited in chemical biology, in two biologically relevant projects. In Aims 1 and 2, we will expand on preliminary results that suggest that redox-active small molecules act as growth factors to induce the growth of Faecalibacterium prausnitzii, an uncultured human gut bacterium. Decreased levels of F. prausnitzii have been implicated in Crohn's disease, but its exact role is unknown due to its inability to be cultured. Aim 1 focuses on the isolation and identification of this growth factor ad Aim 2 focuses on the biological significance of this growth factor. We will apply what we learn in Aims 1 and 2 to a serious human condition: mitochondrial electron transport chain deficiencies, which cause severe, often fatal diseases for which there are no treatments. As these defects lead to perturbations in the flow of electrons in the electron transport chain, we believe that redox-active small molecules may rescue some of these defects.