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Aaron Hoskins, Jennifer Van Os receive Research Forward project funding

Eleven projects were recently selected for funding in the first round of the new Research Forward award competition, including two projects led by CALS PIs. The two CALS-led projects, described in more detail below, are: “Therapeutic targeting of post-transcriptional RNA processing in human diseases” led by Aaron Hoskins in the Department of Biochemistry, and “Mooving Cows: An innovative learning approach using a serious game to improve cow-handling skills in dairy-farm personnel” led by Jennifer Van Os in the Department of Animal and Dairy Sciences.

The Office of the Vice Chancellor for Research and Graduate Education (OVCRGE) hosts the Research Forward initiative to stimulate and support highly innovative and groundbreaking research at the University of Wisconsin–Madison. The initiative is supported by the Wisconsin Alumni Research Foundation (WARF) and will provide funding for 1–2 years, depending on the needs and scope of the project.

Research Forward seeks to support collaborative, multidisciplinary, multi-investigator research projects that are high-risk, high-impact, and transformative. It seeks to fund research projects that have the potential to fundamentally transform a field of study as well as projects that require significant development prior to the submission of applications for external funding. Collaborative research proposals are welcome from within any of the four divisions (Arts & Humanities, Biological Sciences, Physical Sciences, Social Sciences), as are cross-divisional collaborations.

Therapeutic targeting of post-transcriptional RNA processing in human diseases

The RNA copies of DNA genes are heavily edited before they can be used by the cell. Internal sequences are removed by splicing, poly(A) tails added, and the nucleotides themselves are often modified. Small molecule and oligonucleotide drugs that perturb RNA processing are poised to revolutionize medicine.

This project will build upon UW–Madison’s strengths in RNA biology and investments in structural biology to create a multi-disciplinary research program to Drug RNA (DRUGR). The goal of DRUGR is to discover new RNA-based or RNA-targeting therapies for human disease. The project team combines complementary areas of expertise (biochemistry, chemistry, single molecule physics, structural biology) and parallel research tracks to acquire knowledge and meet our goals. As an initial target, the team will focus on identifying small molecule drugs that correct splicing defects due to loss of the LUC7L2 gene in myeloid neoplasms. The goals are to build and benchmark novel DRUGR-STRUCTR and DRUGR-MAP platforms with new discoveries about the biochemistry and structures of LUC7L, LUC7L2, and LUC7L3 proteins. Goldsmith and Hoskins will use massively parallel arrays of RNAs to study binding of the LUC7L proteins to RNAs on the transcriptome scale. By combining these arrays with small molecule drug libraries, compounds will be identified that can rewire cellular RNA processing for therapeutic benefit. Butcher and Grant will use X-ray crystallography and cryo-EM to structurally characterize LUC7 proteins in complex with their RNA binding sites, bound to splicing factors, and in complex with drug candidates. These experiments will provide the foundation for obtaining federal funding for a tiered research enterprise at UW–Madison called The Center for Ribonucleoprotein Research and Drug Discovery.

PRINCIPAL INVESTIGATOR
Aaron Hoskins, associate professor of biochemistry and chemistry, Wasson Professor in Biochemistry of Higher Animals

CO-PRINCIPAL INVESTIGATORS
Samuel Butcher, professor of biochemistry, Steenbock Professor of Biomolecular Structure
Randall Goldsmith, professor of chemistry
Tim Grant, assistant professor of biochemistry and affiliate with the Morgridge Institute for Research

Mooving Cows: An innovative learning approach using a serious game to improve cow-handling skills in dairy-farm personnel

On Wisconsin dairy farms, millions of human-cow interactions occur each day. Handling cows is necessary to harvest milk and provide animal care, but presents a risk of injury to personnel. Furthermore, inappropriate handling of cows impairs animal welfare and milk production and erodes public trust in dairy farming practices. Proper cow handling requires effective training, but existing resources have substantial limitations and lack evidence of effectiveness. Education research has demonstrated that “serious games” produce positive learning outcomes.

This project will create a digital serious game to transform training in farm animal handling. Trainees will practice proper techniques in a simulated setting – safe for both people and cows. Research Forward funding will enable programming and pilot testing of the training tool with dairy farm personnel. This multidisciplinary team comprises experts in animal welfare science, veterinary medicine, social psychology and behavior change, human health, and multilingual education and extension.

PRINCIPAL INVESTIGATOR
Jennifer Van Os, assistant professor of animal and dairy sciences

CO-PRINCIPAL INVESTIGATOR
Nigel Cook, professor and chair of food animal production in medical sciences

CO-INVESTIGATORS
Markus Brauer. Professor of psychology
Olufunmilola Abraham, assistant professor of pharmacy
Dominic Ledesma, interim director of diversity and inclusion for the UW–Madison Division of Extension

CALS personnel are also involved – as co-PIs and co-investigators – in these additional Research Forward-funded projects: