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.

Public Health Relevance

This proposal focuses on applying redox-active small molecules in two projects relevant to human health. First, we will explore the ability of redox-active small molecules to act as growth factors to induce the growth of Faecalibacterium prausnitzii, an uncultured human gut bacterium that has been implicated in Crohn's disease, but whose exact role is unknown due to its inability to be cultured. Second, we will explore the ability of redox-active small molecules to rescue mitochondrial electron transport chain deficiencies, which cause severe, often fatal diseases for which there are no treatments.

Agency
National Institute of Health (NIH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM103010-02
Application #
8732475
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Barski, Oleg
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Harvard Medical School
Department
Biochemistry
Type
Schools of Medicine
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115