Subha R. Das
Assistant Professor of Chemistry
Research Interests
Subha Das is interested in the chemical biology of RNA, the study of the structure and function of RNA and its analogues that are chemically modified with atomic precision. Specifically, Das explores the chemistry of RNA enzymes or ribozymes and the cellular processes they mediate. He is also investigating the interactions of RNA with small molecules and proteins. These interactions are crucial in the expression and regulation of genes. With this knowledge Das seeks to engineer nucleic acids with a view to manipulating gene expression.
Professional Background
Ph.D. Organic Chemistry, Auburn University, Alabama, 2000.
M.Sc. with honors. Organic Chemistry, Birla Institute of Technology & Science, Pilani, India, 1994.
B.E. with honors. Computer Science, Birla Institute of Technology & Science, Pilani, India, 1994.
After earning his doctorate from Auburn University, Das was a postdoctoral Research Associate of the Howard Hughes Medical Institute at the University of Chicago. There he investigated how a ribozyme derived from a human hepatitis virus catalyzes chemical reactions required for its replication. He joined the Carnegie Mellon Department of Chemistry as an assistant professor in 2006.
Why is it important to study RNA? What is RNA chemical biology?
The number of genes in an organism does not determine its complexity – corn, for example, has nearly twice as many genes as humans. Genes are merely the protein encoding portions of an organism's DNA. Most of this DNA however, is first converted to RNA. Therefore RNA holds the key to the complexity that arises from the expression and regulation of genes. So it becomes important to study RNA to understand how it contributes to cellular function and an organism's complexity.
In order to explore further the biological possibilities of RNA, we need to understand the chemical capabilities and reactivities of this biopolymer. Synthetic chemistry allows us to manipulate the chemical composition of RNA and nucleic acids while biochemical and biophysical techniques can shed light on how the parts of RNA interact in a biological context.
What are ribozymes and riboswitches and what do they do?
Enzymes that are composed of RNA are referred to as ribozymes. Although limited to only the four RNA nucleobases (A, C, G and U) ribozymes can still catalyze chemical reactions just like protein enzymes, which have a much greater range of functional groups. Ribozymes are great model systems for studying how RNA can form structures that mediate chemical changes.
Riboswitches are segments of RNA that bind small molecules and change the way a gene is expressed into protein products. While man-made nucleic acid aptamers that bind other molecules are well known, naturally occurring riboswitches are a recently discovered mechanism by which RNA exerts control over gene expression. A focus of my research is studying how the RNA interacts with small molecules and proteins and to engineer ribozymes, aptamers and riboswitches to bind to unnatural small molecules and thereby control gene expression.
Does the study of RNA, ribozymes and riboswitches have biomedical uses or applications?
Yes. RNA and nucleic acids research is making a tremendous impact on biomedical science. The knowledge of RNA related processes at an atomic level could eventually be used to control cellular processes. This would in turn help us to suppress cancer and viral expression at the cellular and systemic levels. RNA and its derivatives are being used to target and degrade sequence specific messages from genes – thus we can shut down specific genes from viruses or aberrant genes that cause cancer. Chemically altering riboswitches would allow scientists not only to “switch off” harmful genes but also to “switch on” favorable ones. Sensors designed from nucleic acids and RNA can help in the diagnosis of cellular events and processes. Ultimately an understanding of RNA chemistry will help us fathom cellular processes such as the response to infectious agents or harmful environmental factors.
What attracted you to Carnegie Mellon’s faculty?
The interdisciplinary science and an environment that fosters collaboration. Combining expertise is a very powerful approach to tackling modern scientific problems and this always advances the quality of research. I'm looking forward to fruitful collaborations with colleagues at Carnegie Mellon.
Matthew R. Bittel
June 15, 2006
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