Information in our cells—the instructions for making the molecules, cells and organs that make us who we are—is stored in the sequence of our DNA, our genes. That information is expressed as RNA, which is translated into the proteins that actually make our cell work. Just as important as the content of the information stored in our DNA is the regulation of its expression. Genetic regulation of expression is programed by the sequence of our genes and is the basis of inheritance, allowing different organisms to have different traits based on their different DNA sequence. Epigenetic regulation acts in situation in which the DNA is the same, but the expression patterns are different. These situations are often developmental, such as when muscle and fat cells develop from the same embryonic tissue, but express very different genes. Epigenetic regulation can also control trans-generation inheritance of gene expression patterns, so that a parents environment can regulate a child's gene expression, without affecting their DNA sequence. Understanding all of these aspects of gene regulation is essential for understanding how molecules build cells and cells build organisms.
The study of DNA, RNA and epigenetics in the Department of Biochemistry and Molecular Pharmacology broadly encompasses how the information in DNA is replicated and repaired, how its expression as RNA is regulated at the levels of RNA synthesis, maturation, stability and translation, and how that expression is regulated, both genetically and epigenetically.
The Kelch and Rhind labs study the replication and repair of DNA, trying to understand the mechanisms that ensure it is faithfully inherited in future generations, with the Kelch lab using biochemical and structural methods to elucidate the mechanisms of the DNA replication machinery, with special emphasis on the DNA polymerase sliding clamp and clamp loader complexes and the Rhind lab focusing on the regulation of DNA replication kinetics in vivo.
The Schiffer lab studies enzymes that edit DNA, with the Schiffer lab focusing on the APOBEC3 cytidine deaminases and the Hepatitis C NS3/4A helicase to develop more specific anti-viral therapeutics.
The Rando, Sagerström and Thompson labs study the genetic and epigenetic regulation of gene expression, with the Rando lab focusing on chromatin structure and function in budding yeast and the role of epigenetic information carriers in sperm as mediators paternal effects of diet in mouse, the Sagerström lab studying the transcriptional regulation of gene expression during neurogenesis and how TALE factors act as ‘pioneer’ transcription factors to regulate key determinants of neuronal development, and the Thompson lab developing therapeutics targeting the enzymes that contribute to the epigenetic control of gene transcription, including the Protein Arginine Deiminases, which have been shown to play roles in a variety of inflammatory diseases and cancer.
The Massi, Munson, Ryder labs study the regulation of RNA after it has been transcribed, with the Massi and Ryder labs collaborating on the biophysics and cellular biochemistry, respectively, of how RNA binding proteins regulate RNA stability and translation, and Munson lab studying a novel nuclear export pathway in yeast.
UMass is on the cutting edge of international research in the study of DNA, RNA and epigenetics. Our department has contributed to many major recent advances including the the contributions of the Dekker and Weng labs to our understanding of structure and functional composition of the genome, both through there own work and their leadership in the ENCODE project, the work in the Ryder lab to understand the post-transcriptional regulation of RNA via RNA splicing and translational control, and the work of the Rando lab on trans-generational inheritance.
The Department of Biochemistry and Molecular Pharmacology is also pushing the envelope in the structural biology of DNA metabolism and gene expression with the establishment of the Massachusetts Facility for High-Resolution Electron Cryo-Microscopy driven in large part by the efforts of the Kelch and Schiffer labs.
| Job Dekker
|| Brian Kelch
|Francesca Massi||Mary Munson||Thoru Pederson|
|Oliver Rando|| Nick Rhind
| Charles Sagerström
|| Celia Schiffer
|Zhiping Weng||Jill Zitzewitz|