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Concerns about systemic racism at academic and research institutions have increased over the past decade. Here, we investigate data from the National Science Foundation (NSF), a major funder of research in the United States, and find evidence for pervasive racial disparities. In particular, white principal investigators (PIs) are consistently funded at higher rates than most non-white PIs. Funding rates for white PIs have also been increasing relative to annual overall rates with time. Moreover, disparities occur across all disciplinary directorates within the NSF and are greater for research proposals. The distributions of average external review scores also exhibit systematic offsets based on PI race. Similar patterns have been described in other research funding bodies, suggesting that racial disparities are widespread. The prevalence and persistence of these racial disparities in funding have cascading impacts that perpetuate a cumulative advantage to white PIs across all of science, technology, engineering, and mathematics.

The political power of Asian Americans and Pacific Islanders (AAPIs) has increased steadily in the United States. By 2040, one in ten Americans will be AAPI, and the number of Asian Americans registered to vote will have doubled (Ong, Ong and Ong, 2015). This section examines the growing AAPI electorate and projects a trajectory for AAPI civic engagement and political participation from now until 2040. By looking at trends and projections for citizenship, voter registration, voter turnout, elected officials, and political infrastructure, the authors illustrate that AAPI political empowerment will have even a greater influence on the future of American politics.

Cofilin is a member of the actin depolymerizing factor (ADF)/cofilin family of proteins. It plays a key role in actin dynamics by promoting disassembly and assembly of actin filaments. Upon its binding, cofilin has been shown to bridge two adjacent protomers in filamentous actin (F-actin) and promote the displacement and disordering of subdomain 2 of actin. Here, we present evidence for cofilin promoting a new structural change in the actin filament, as detected via a switch in cross-linking sites. Benzophenone-4-maleimide, which normally forms intramolecular cross-linking in F-actin, cross-links F-actin intermolecularly upon cofilin binding. We mapped the cross-linking sites and found that in the absence of cofilin intramolecular cross-linking occurred between residues Cys374 and Asp11. In contrast, cofilin shifts the cross-linking by this reagent to intermolecular, between residue Cys374, located within subdomain 1 of the upper protomer, and Met44, located in subdomain 2 of the lower protomer. The intermolecular cross-linking of F-actin slows the rate of cofilin dissociation from the filaments and decreases the effect of ionic strength on cofilin-actin binding. These results are consistent with a significant role of filament flexibility in cofilin-actin interactions.

Cofilin is a member of the actin depolymerizing factor (ADF)/cofilin family of proteins. It plays a key role in actin dynamics by promoting disassembly and assembly of actin filaments. Upon its binding, cofilin has been shown to bridge two adjacent protomers in filamentous actin (F-actin) and promote the displacement and disordering of subdomain 2 of actin. Here, we present evidence for cofilin promoting a new structural change in the actin filament, as detected via a switch in cross-linking sites. Benzophenone-4-maleimide, which normally forms intramolecular cross-linking in F-actin, cross-links F-actin intermolecularly upon cofilin binding. We mapped the cross-linking sites and found that in the absence of cofilin intramolecular cross-linking occurred between residues Cys374 and Asp11. In contrast, cofilin shifts the cross-linking by this reagent to intermolecular, between residue Cys374, located within subdomain 1 of the upper protomer, and Met44, located in subdomain 2 of the lower protomer. The intermolecular cross-linking of F-actin slows the rate of cofilin dissociation from the filaments and decreases the effect of ionic strength on cofilin-actin binding. These results are consistent with a significant role of filament flexibility in cofilin-actin interactions.

Rapid remodeling of the actin cytoskeleton is essential for many cellular processes including cell growth, differentiation, division, and motility. Actin dynamics is expedited by various actin-binding proteins, with Spire and cofilin being prominent among them. In vitro, Spire and cofilin are able to sever, nucleate, and depolymerize filaments, albeit by different methods. This dissertation focuses on characterizing the mechanisms of Spire and cofilin interactions with actin and studying their roles in actin dynamics. We first study the complex role of Spire in actin dynamics. We observe that the severing activity of Spir is weak and conclude that rapid actin depolymerization is mainly due to the sequestering activity of Spir. Polymerization assays show that Spir and actin form complexes that accelerate polymerization, when present at low stoichiometries, but suggest their heterogeneity. Notably, Spir does not bind readily four actin monomers in a stable complex. Similarly, depolymerization of actin by Spir leads to the formation of several types of their complexes. Strikingly, as detected by cross-linking experiments, Spir induces the formation of lateral actin-actin complexes in addition to the expected longitudinal complexes. The formation of these structures is not affected by the presence of Cappuccino. Finally, using yeast actin mutants labeled with fluorescent probes, we detected different affinities of Spir domains for actin protomers. Together, our data suggest that Spir-actin interactions are more complex than originally believed. Next, we examined the effects of cofilin isoforms on the dynamics of actin isoforms. First, we studied the change in the persistence length of both vertebrate and yeast F-actin upon binding of human and yeast cofilin. We observe that human cofilin-1 (hCof1) binds to yeast actin filaments but neither increases their flexibility nor severs them. In contrast to that, yeast cofilin increases the flexibility of skeletal and yeast acti

Rapid remodeling of the actin cytoskeleton is essential for many cellular processes including cell growth, differentiation, division, and motility. Actin dynamics is expedited by various actin-binding proteins, with Spire and cofilin being prominent among them. In vitro, Spire and cofilin are able to sever, nucleate, and depolymerize filaments, albeit by different methods. This dissertation focuses on characterizing the mechanisms of Spire and cofilin interactions with actin and studying their roles in actin dynamics. We first study the complex role of Spire in actin dynamics. We observe that the severing activity of Spir is weak and conclude that rapid actin depolymerization is mainly due to the sequestering activity of Spir. Polymerization assays show that Spir and actin form complexes that accelerate polymerization, when present at low stoichiometries, but suggest their heterogeneity. Notably, Spir does not bind readily four actin monomers in a stable complex. Similarly, depolymerization of actin by Spir leads to the formation of several types of their complexes. Strikingly, as detected by cross-linking experiments, Spir induces the formation of lateral actin-actin complexes in addition to the expected longitudinal complexes. The formation of these structures is not affected by the presence of Cappuccino. Finally, using yeast actin mutants labeled with fluorescent probes, we detected different affinities of Spir domains for actin protomers. Together, our data suggest that Spir-actin interactions are more complex than originally believed. Next, we examined the effects of cofilin isoforms on the dynamics of actin isoforms. First, we studied the change in the persistence length of both vertebrate and yeast F-actin upon binding of human and yeast cofilin. We observe that human cofilin-1 (hCof1) binds to yeast actin filaments but neither increases their flexibility nor severs them. In contrast to that, yeast cofilin increases the flexibility of skeletal and yeast acti