Supplement funds are requested under PA-18-591 and NOT-GM-20-013 to purchase a BD FACS Melody cell sorting instrument. The system will support NIGMS award R35GM118166. Research in this award emphasizes the interface between structural biology, molecular biophysics, and immunology. Broadly speaking, work in this project strives to connect the fundamental biophysical principles that govern protein behavior with molecular recognition in the immune system. This work is also instructional for understanding the basic rules of molecular recognition and elucidating principles for protein modeling and design in complex systems. Major amounts of work in the project now relies on library screening. This is used to identify mutations which govern specificity, to understand how specificity and affinity can be altered, and to identify which targets are recognized and which are not. The screening processes rely on fluorescent activated cell sorting. Technology currently available to the laboratory is aging, unnecessarily complex, requires advance scheduling, and necessitates paying expensive user fees. The streamlined, single laboratory system requested here will permit more a rapid advance towards the project goals. 85% of the system cost is requested from NIGMS. The remaining 15% will be contributed by the University of Notre Dame.

Public Health Relevance

Supplement funds are requested under PA-18-591 and NOT-GM-20-013 to purchase a BD FACS Melody cell sorting instrument for NIGMS funded research on which PI Brian Baker serves as the principal investigator. This instrument will facilitate research into complex molecular recognition phenomena in the immune system and provide insight into how immune recognition contributes to human health and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
3R35GM118166-05S1
Application #
10131481
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Koduri, Sailaja
Project Start
2016-05-01
Project End
2021-04-30
Budget Start
2020-05-01
Budget End
2021-04-30
Support Year
5
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Notre Dame
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
824910376
City
Notre Dame
State
IN
Country
United States
Zip Code
46556
Spear, Timothy T; Wang, Yuan; Smith Jr, Thomas W et al. (2018) Altered Peptide Ligands Impact the Diversity of Polyfunctional Phenotypes in T Cell Receptor Gene-Modified T Cells. Mol Ther 26:996-1007
Riley, Timothy P; Hellman, Lance M; Gee, Marvin H et al. (2018) T cell receptor cross-reactivity expanded by dramatic peptide-MHC adaptability. Nat Chem Biol 14:934-942
Wang, Yuan; Singh, Nishant K; Spear, Timothy T et al. (2017) How an alloreactive T-cell receptor achieves peptide and MHC specificity. Proc Natl Acad Sci U S A 114:E4792-E4801
Borrman, Tyler; Cimons, Jennifer; Cosiano, Michael et al. (2017) ATLAS: A database linking binding affinities with structures for wild-type and mutant TCR-pMHC complexes. Proteins 85:908-916
Spear, Timothy T; Wang, Yuan; Foley, Kendra C et al. (2017) Critical biological parameters modulate affinity as a determinant of function in T-cell receptor gene-modified T-cells. Cancer Immunol Immunother 66:1411-1424
Ayres, Cory M; Corcelli, Steven A; Baker, Brian M (2017) Peptide and Peptide-Dependent Motions in MHC Proteins: Immunological Implications and Biophysical Underpinnings. Front Immunol 8:935
Ayres, Cory M; Riley, Timothy P; Corcelli, Steven A et al. (2017) Modeling Sequence-Dependent Peptide Fluctuations in Immunologic Recognition. J Chem Inf Model 57:1990-1998
Singh, Nishant K; Riley, Timothy P; Baker, Sarah Catherine B et al. (2017) Emerging Concepts in TCR Specificity: Rationalizing and (Maybe) Predicting Outcomes. J Immunol 199:2203-2213
Baker, Brian M; Evavold, Brian D (2017) MHC Bias by T Cell Receptors: Genetic Evidence for MHC and TCR Coevolution. Trends Immunol 38:2-4
Blevins, Sydney J; Baker, Brian M (2017) Using Global Analysis to Extend the Accuracy and Precision of Binding Measurements with T cell Receptors and Their Peptide/MHC Ligands. Front Mol Biosci 4:2

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