Discovering amyloid-forming
chemical space
We are interested in the effect of cellular environmental factors for promoting or blocking amyloid formation for a selected panel of known functional and pathological amyloid-forming proteins. Selected proteins will be screened against cellular cofactors, metabolites, and osmolytes
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Discovering amyloid-forming
chemical space
We are interested in the effect of cellular environmental factors for promoting or blocking amyloid formation for a selected panel of known functional and pathological amyloid-forming proteins. Selected proteins will be screened against cellular cofactors, metabolites, and osmolytes
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Our Research
Amyloids are highly stable protein aggregates. While they are typically implicated in causing disease, such as neurodegeneration and cancer, they can also perform important cellular functions. The Carroll lab team is fascinated by the role of cellular factors in regulating formation of amyloids - both pathological and functional! We are working on a wide range of projects centered around understanding the amyloid formation process for cancer-associated and immune signaling proteins. Our projects investigate how different factors in the cellular environment block or promote amyloid formation in vitro and how the addition of a common posttranslational modification, ubiquitin, alters the amyloid-forming landscape. We are especially interested in how these factors may differ between amyloids associated with disease and amyloids associated with cellular function. Our long-term goal is to uncover the mechanisms by which crosstalk between diverse cellular components can tip the scales towards or against amyloid formation.
Discovering amyloid-forming
chemical space
We are interested in the effect of cellular environmental factors for promoting or blocking amyloid formation for both proteins associated with pathology (e.g., amyloid formation leads loss of function phenotypes in cancer) and functional processes (e.g., amyloid formation regulates crucial cellular processes) . Towards this goal, we screen diverse cellular cofactors, metabolites, and osmolytes to understand their interactions with our favorite target proteins.
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Measuring the effect of ubiquitin on
amyloid-forming proteins
Ubiquitin is a protein posttranslational modification that targets proteins to the cell's trash can, the proteasome, for degradation. Ubiquitin can destabilize, or unfold, the protein it is attached to, promoting proteasomal engagement, or have no effect on the target, hindering proteasomal degradation. The Carroll lab is developing new, high-throughput technologies for profiling the biophysical effects of ubiquitination on amyloid-forming proteins to map out the role this critical hub of the proteostasis network plays in amyloid formation.
Biophysical and functional characterization of ubiquitin-modified proteins
We are interested in the conformational and functional consequences of ubiquitination on our proteins of interest. We use our toolkit of biophysical assays to quantify ubiquitin-induced destabilization and monitor conformation, as well as functional readouts of in vitro proteasomal degradation rates, substrate-proteasome interactions, and enzymatic activity.