1. Compartmentalized Free NAD+

 

What are the structural mechanisms that regulate the function of the human mitochondrial NAD+ transporter, and how is activity controlled?

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2. Determining Critical Thresholds in Disease

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How do fluctuations in the levels of mitochondrial NAD+ alter cellular homeostasis? Can we target the transporter to modulate mitochondrial NAD+ levels and ameliorate disease?

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3. Technology Development

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The power of genetically-encoded in situ NAD+ biosensors has been demonstrated by its role in revealing new biology and regulation (1), (2): Can we use design principles to optimize the current single-fluorescent-protein NAD+ biosensor and to develop new sensors for other intracellular metabolites?