The Mura Lab employs both experimental and computational
approaches to understand the structure, function/dynamics, and evolution of
RNA– and DNA–based protein assemblies.
In particular, we seek a deeper understanding of ribonucleoprotein
(RNP) assemblies built upon a scaffold of 'Sm' proteins — What these protein/RNA
complexes look like at atomic resolution (structure), their assembly pathways
and dynamical behavior (function), and the interrelationships between Sm and
Sm-like systems (evolution).
Sm proteins were discovered as the antigens in the autoimmune disease lupus, and
are now known to form a broad, evolutionarily-conserved family that plays
pivotal roles in most aspects of RNA metabolism (including mRNA splicing), as
well as in bacterial cell···cell communication networks (“quorum sensing”).
Sm-based complexes such as the ‘spliceosome’ exceed the ribosome in terms of
both size and architectural complexity, thereby providing an immensely rich area
for ongoing studies. Current work focuses on Sm systems drawn from both a
well-established context (splicing) and a more recently emerging area (quorum
sensing) that is of major biomedical significance because of its involvement in
biofilm-mediated bacterial pathogenesis. The research program being developed to
pursue this work is necessarily highly interdisciplinary, relying particularly
heavily on methodologies from structural biology (e.g., crystallography),
bioinformatics (e.g., statistical and phylogenetic methods for protein family
analysis), and computational biochemistry (e.g., molecular dynamics
simulations), in addition to traditional wet-lab biochemistry.
A more graphical summary of our chief interests and approaches: