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Research

Overview

The broad interest of the Fuchs lab is to understand the role of protein sequence, composition, and modification state in determining protein function. We are therefore interested in the protein chemistry and biological function of all proteins – from very simple, repetitive peptide sequences to large protein complexes. This broad interest is borne out in two major research focuses: repetitive proteins and chromatin.

Repetitive proteins represent an interesting biological problem. Many have conserved function, but given that repeat domains are typically inherently unstable at the genetic level, they are prone to repeat expansion, contraction, and mutation. We hypothesize that this instability provides an important evolutionary mechanism for tuning repeat protein function. Our work on repetitive protein biology covers many levels of analysis, from bioinformatic identification of repetitive domains to in vitro biochemical characterization to in vivo mutant phenotyping, and even protein neofunctionalization through repetitive domain engineering. The workhorse organisms for these studies are the yeast S. cerevisiae and its distant cousins C. glabrata and S. pombe, which give us fast and flexible genetic systems with which to work.

Chromatin, at its basic unit, is made up of histone proteins and DNA. Because this packaging results in a natural barrier to gene expression, chromatin state often has profound regulatory impacts on expression. Chromatin state can be controlled by post-translational modification of histone proteins or by other chromatin-associated enzymes or structural proteins. Because of its regulatory ability, chromatin often undergoes dynamic changes during the key biological processes, such as development, regeneration, and aging. We are investigating the role of chromatin during aging in yeast, regeneration in planaria, and development in frogs.

Our research is currently funded by:

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