Daniel Becker - US grants

Wildlife are fed by humans intentionally or accidentally all over the world. This common activity can change wildlife physiology and behavior, intensify human-wildlife interactions, and influence human health through the transmission of infectious disease. This research will examine how feeding wildlife influences the spread of infectious disease, focusing on vampire bats and rabies virus. It will develop models that can a) forecast the future spread of rabies when livestock rearing expands into undisturbed habitats and b) predict human and animal rabies risk in areas undergoing rapid land conversion. Results could alter societal views on activities ranging from bird feeders to ecotourism and will directly improve predictions of the spread of a lethal disease. The project will support education and training of a doctoral student in modern molecular biology techniques and will develop new tools for evaluating disease in bats.

The research will integrate observed relationships between livestock abundance, antiviral immunity, and bat dispersal between colonies into mathematical models of rabies transmission. Earlier research showed that livestock rearing is associated with higher chronic stress, lower antibody levels, and larger vampire bat colonies, suggesting that livestock rearing produces source populations of immune-impaired vampire bats. The first research goal will use novel immunological tools on field-collected samples to characterize expression of antiviral cytokines of vampire bats across a livestock density site gradient in two regions. These data will be used to test if bats in livestock-dense habitat invest more or less in responses that promote resistance to rabies virus. The project's second goal will use molecular genetics approaches to characterize the connectivity of bat populations at fine spatial scales through field-collected tissue samples. Results will determine whether or not bat movement varies with livestock distribution. Finally, the researchers will develop a spatially explicit mathematical model of rabies transmission that incorporates results from the first two goals to provide a mechanistic framework for understanding how resource heterogeneity affects viral spread.

This National Science Foundation Research in Undergraduate Institutions award from the Chemistry of Life Processes Program funds Dr. Misty L. Kuhn from San Francisco State University (SFSU) and Dr. Daniel P. Becker from Loyola University Chicago to create biochemical tools to study enzymes in the family of Gcn5-related N-acetyltransferase (GNAT) proteins of unknown function from the soil microorganism, Pseudomonas aeruginosa. Specifically, these tools are used in combination with structure determinations via X-ray crystallography to gain a greater understanding of how molecules bind to GNATs. Since relatively little is known about the structure/function relationship of GNATs from P. aeruginosa, this work fills this gap in knowledge. Determining these functions is important because human welfare depends on healthy agriculture. This project enhances the research infrastructure at SFSU by establishing its first protein crystallization resource and increasing the repertoire of sophisticated biochemistry skills of underrepresented minority and disadvantaged undergraduate students.
 
The goal of this project is to improve the functional annotation of P. aeruginosa GNATs of unknown function using a combination of protein X-ray crystallography, molecular modeling, organic synthesis, and enzymology. The architecture of the acceptor site of several GNAT proteins are probed using biochemical tools and X-ray crystallography. Active site residues that are critical for catalysis and substrate specificity are identified and tested using molecular modeling, site-directed mutagenesis, and enzyme kinetics. The results of this project provides the foundational knowledge to categorize experimentally uncharacterized members of the GNAT family and improve computational functional annotation of GNATs of unknown function.

This National Science Foundation Research in Undergraduate Institutions award from the Chemistry of Life Processes Program funds Dr. Misty L. Kuhn from San Francisco State University (SFSU) and Dr. Daniel P. Becker from Loyola University Chicago to create biochemical tools to study enzymes in the family of Gcn5-related N-acetyltransferase (GNAT) proteins of unknown function from the soil microorganism, Pseudomonas aeruginosa. Specifically, these tools are used in combination with structure determinations via X-ray crystallography to gain a greater understanding of how molecules bind to GNATs. Since relatively little is known about the structure/function relationship of GNATs from P. aeruginosa, this work fills this gap in knowledge. Determining these functions is important because human welfare depends on healthy agriculture. This project enhances the research infrastructure at SFSU by establishing its first protein crystallization resource and increasing the repertoire of sophisticated biochemistry skills of underrepresented minority and disadvantaged undergraduate students.
 
The goal of this project is to improve the functional annotation of P. aeruginosa GNATs of unknown function using a combination of protein X-ray crystallography, molecular modeling, organic synthesis, and enzymology. The architecture of the acceptor site of several GNAT proteins are probed using biochemical tools and X-ray crystallography. Active site residues that are critical for catalysis and substrate specificity are identified and tested using molecular modeling, site-directed mutagenesis, and enzyme kinetics. The results of this project provides the foundational knowledge to categorize experimentally uncharacterized members of the GNAT family and improve computational functional annotation of GNATs of unknown function.

The Viral Emergence Research Initiative Biology Integration Institute (VERENA BII) will integrate data and biological theory across the fields of microbiology, immunology, ecology, evolution, and global change biology, working towards a unified understanding that improves our ability to predict viral emergence. The COVID-19 pandemic highlights a pressing need to understand the ecology and evolution of emerging viruses. These global dynamics are determined first and foremost by the genetic code of both viruses and their hosts, and by microscopic interactions between the two at the level of proteins and cells. However, biologists frequently struggle to connect theory across these scales. At the heart of this research effort is an open clearinghouse of big data, creating new opportunities to apply artificial intelligence to real-world problems. To foster a core set of data fluency and interdisciplinary research skills, the Lighthouse Learning Community will train participants at every career stage in the boundary-spanning science of the host-virus network, including more than 100 early career scientists. Undergraduates will be introduced to both biology and data science through a Course-based Undergraduate Research Experience in “The Fundamentals of Disease Surveillance,” while graduate students and postdoctoral fellows will explore these methods deeper through a biology integration workshop series, including a new Summer in the Capitol program in Washington, D.C. This cohort of emerging scholars will use open source materials, K-12 outreach, and digital media to harness public interest in emerging diseases like COVID-19, raising awareness about key issues while sharing the importance of basic biological research to save lives and protect ecosystems.<br/><br/>To identify the mechanistic and molecular Rules of Life that govern host-virus dynamics at planetary scales, the VERENA BII will leverage a unique mix of data synthesis, computational innovation, field sampling, and laboratory experiments to identify the molecular underpinnings of host-virus interactions. An unprecedented comparative study of the chiropteran within-host environment will generate and test hypotheses about the immunological adaptations that allow bats to tolerate deadly viruses. In parallel, model-guided experiments will measure the features of the invertebrate immune system that play the greatest role in mosquitoes’ competence as arboviral vectors. Together, these model systems will illuminate the hard-coded basis of host-virus compatibility, supporting new machine learning methods to predict ecological and evolutionary networks and anticipate global risks of viral emergence in a changing climate. More broadly, the VERENA BII will expand an existing role as a hub of open data, software, and cyberinfrastructure for host-virus interactions, experimental virology, and wildlife disease surveillance.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.