Karndeep Singh

Biochemistry and Molecular Biology

Area of Doctoral Study: Biochemistry
Undergraduate Institute: University of Maryland, Baltimore County (UMBC)

Research Advisor: Michael Summers, Ph.D.

Description of Research

My primary thesis project investigates the underlying molecular mechanisms between 5′-capped RNAs of the human immunodeficiency virus type-1 (HIV-1) RNA genome and a cellular cap binding protein, eIF4E, using nuclear magnetic resonance spectroscopy and biochemical techniques. One major difficulty of my project is the ability to synthesize and purify highly pure 5′-capped RNAs reliably in vivo. My team and I have developed a novel method using a DNA splint to successfully purify 5′-capped RNAs in the laboratory. After purifying the HIV-1 5′-capped RNAs, I have tested binding of the 5′-capped RNAs to eIF4E and have determined that HIV-1 RNA transcripts bind significantly tighter to the cap binding protein. Currently, I am working to solve the first structure of eIF4E interacting with a 5′-capped RNA using NMR spectroscopy. My findings suggest novel interactions of cap-dependent translational machinery with the monomeric HIV-1 RNA genome and could elucidate how the HIV-1 RNA genome manipulates endogenous translational machinery to ensure production of its own viral proteins. Throughout my graduate studies, I have had the honor to mentor and train nine undergraduate students and three high school students who have been instrumental to my development as a scientist and mentor but also instrumental to overcoming the challenges of my project.