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: