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Faculty & Research
Department of Biology
200 Boston Ave., Suite 4743
Medford, MA 02155
Email Dr. Fuchs
Stephen M. Fuchs
B.A. Chemistry, Penn State University - 1999
Graduate Research Area: Genetics and Molecular Biology
In the Fuchs lab we want to know how the composition of a protein dictates both its structure and its function. This interest runs the gamut of protein chemistry from understanding the biology of very simple, repetitive peptide sequences to dissecting the interactions of large protein complexes.
Currently our research is focused on two main areas - Post-translational modifications (PTMs) of proteins and the biology of repetitive protein domains. We emphasize creative thinking and cross-disciplinary approaches to answer questions regarding protein structure and function. We employ a broad spectrum of tools and systems from fluorescence microscopy, chemical synthesis, and biophysical methods to classical yeast genetics and mammalian cell culture.
The Fuchs lab has two primary missions: to educate and train the next generation of scientists and to advance our understanding of the factors that regulate protein function with the hope to develop potentially useful materials and therapeutics.
Post-translational modifications: Key regulators of development, cell division, and disease
Fifteen of the twenty canonical amino acids can be chemically modified in vivo, either by enzymes or small molecules, after they have been incorporated into a protein sequence. To date, more then 300 different modifications have been described — relating to nearly every aspect of biology. PTMs serve to alter many aspects of a protein's function including: where it resides in the cell, what it interacts with, how long it remains functional, and the extent of its activity. Nearly every day systems-wide proteomics studies are uncovering new PTMs associated with specific diseases or cell states although the function of most modifications remains a mystery. In the Fuchs lab we are working to: 1) develop methodology to probe the function of PTMs, and 2) understand the role of PTMs in regulating processes. Currently, we have a particular interest in PTMs of histone proteins and their roles in regulating transcription and other DNA-templated processes.
Repetitive protein domains: Important regulatory sequences or byproducts of polynucleotide expansion
Eukaryotic genomes are littered with repetitive DNA sequences. The repetitive nature of these sequences makes them unstable to processes such as replication and recombination resulting in a high frequency of expansion/contraction, recombination and DNA damage. As such, repetitive DNA elements are associated with a number of genetic disorders including Huntington's disease, fragile X syndrome, and a number of neuromuscular ataxias (See the Mirkin and Freudenreich labs at Tufts). However, more than 50% of eukaryotic proteins are also predicted to have repetitive protein sequences (derived from repetitive DNA elements), many of which are evolutionarily concerned. This suggests these repetitive regions do more than just cause disease and may also play functional regulatory roles in cells. One well-studied example is the repetitive C-terminal domain (CTD) of RNA polymerase II (RNAPII). This heptapeptide sequence (YSPTSPS) is tandemly repeated between 26 and 52 times in all eukaryotes from yeast to humans and functions as a scaffold for the association of numerous transcription-associated factors. We are interested in understanding how these repetitive protein sequences evolved, how the number of repeats is regulated, and what functions they are playing in the cell.
The Fuchs lab offers a unique training environment for those interested in understanding biological problems from chemical, biochemical, and cytological perspectives. Those interested in learning more should contact Dr. Fuchs at firstname.lastname@example.org.
*** Potential Postdoc Opportunity — The Fuchs lab potentially has a postoc position available for a highly-motivated Ph.D. preferably with a background in synthetic chemistry or chemical biology. Interested applicants should have some experience with peptide chemistry, an interest in learning new biochemical skills, and a desire to train students at both the undergraduate and graduate level. Those interested in learning more should send a CV at email@example.com.
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