The Siltberg-Liberles Lab
Evolution of Protein Structure and Function
conformational flexibility, functional divergence, and molecular mimicry
We perform research in different areas of computational biology, in a comparative, evolutionary fashion. With an emphasis on understanding how protein structure and function have shaped the genomic sequence library of today, we pursue projects aimed at elucidating novel mechanisms of molecular evolution that contribute to biological divergence among, and within a, species. We are particularly interested in how changes in structural properties in protein families contribute to functional divergence.
Evolution of protein structure - we investigate how intrinsic disorder evolves, the evolutionary dynamics of protein structure, and how the interplay between different structural and functional properties influences sequence evolution. Ultimately, we aim to gain insights to better predict functional implications of missense mutations. We also use protein family evolution including structural properties to survey viral protein families for fitness critical regions that may serve as broadly neutralizing antiviral targets.
Molecular mimicry between viruses and their hosts - we explore how viruses are able to mimic structure and sequence for small parts of their host's proteome and the potential consequences thereof. Molecular mimicry between antigenic proteins such as Spike from SARS-CoV-2 and human proteins may trigger the release of cross-reactive antibodies with autoimmune potential. Further, we study how viruses can also use molecular mimicry to interfere with the host cell machinery. We aim to understand how the structural properties of molecular mimicry impact virus-host interactions.
Bioinformatics research in education - we offer Course-based Undergraduate Research Experiences (CUREs) including applications for an integrated analysis of protein sequence data illuminating structural and functional characteristics in an evolutionary context targeted to the non-bioinformatician biology student. Projects in the classroom tend to focus on viruses, cancer genomics, or personal genomics. We assess student learning, self-efficacy, and attitudes in bioinformatics and perform bioinformatics education research to better understand how to make bioinformatics accessible and attractive to biology students. We use bioinformatics CUREs to increase access to research for undergraduate students and study the impact of such interventions. Lastly, we work with high school teachers to boost high school biology curricula with bioinformatics.
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