Thomas D. Grant PhD

Thomas Grant

Thomas D. Grant
PhD

Assistant Professor

Department of Structural Biology

Jacobs School of Medicine & Biomedical Sciences


Specialty/Research Focus

Computational Drug Discovery; Protein Function and Structure

Contact Information
955 Main Street
Room 5156
Buffalo, New York 14203
Phone: 716-829-5490
tdgrant@buffalo.edu



Professional Summary:

My research focus is the development of new methods of analysis in structural biology. My lab uses tools such as X-ray crystallography and small angle scattering to probe the structure and dynamics of biological macromolecules such as proteins and nucleic acids. Our approaches include developing new computational algorithms to analyze data and using cutting edge technologies such as X-ray free electron lasers (XFELs) to collect data on ultrafast time-scales. By developing these tools, we can build pictures and movies of biological molecules to help understand how they perform their functions in the cell. These insights not only help drive advancements in basic science but also help in the design of new drugs for treating diseases.

Education and Training:

  • PhD, Structural and Computational Biology, University at Buffalo (2013)
  • BS, Mathematical Physics, University at Buffalo, Magna Cum Laude (2007)

Employment:

  • Assistant Professor, Structural Biology, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (2020-present)
  • Research Assistant Professor, Structural Biology, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (2018–2020)
  • Research Scientist, BioXFEL, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (2014–2018)
  • Postdoctoral Research Associate, Structural Biology, Hauptman-Woodward Institute (2013–2014)

Awards and Honors:

  • Sidhu Award for Significant Contributions to the Science of Crystallography and/or Diffraction (2013)
  • 2013 Dean’s Distinguished Thesis Award (2013)
  • Margaret C. Etter Student Lecturer Award (2011)
  • Honorable Mention Recipient, NSF Graduate Research Fellowship Program (2009)

Research Expertise:

  • Iterative phasing for solution scattering: We develop algorithms that solve the phase problem for solution scattering. This provides 3D electron density maps from the 1D solution scattering profiles, giving insights into particle shape at low-resolution.
  • Serial crystallography: Serial crystallography is a type of X-ray crystallography technique that uses X-rays to take diffraction snapshots of hundreds of thousands of microcrystals in succession to build up a complete 3D diffraction pattern. This technique is most often done with X-ray free electron lasers, but can also be done with synchrotrons. We often perform serial crystallography experiments for both soluble and membrane proteins. This is one of the few approaches that is capable of determining the high-resolution structures of membrane proteins and is amenable to time-resolved studies.
  • Solution Scattering: We use solution scattering to probe the low-resolution structure of macromolecules in aqueous solution. These data are highly complementary to other structural techniques that provide high-resolution data such as X-ray crystallography, NMR and cryoEM.
  • Time-resolved X-ray scattering: We use ultrafast time-resolved X-ray scattering with X-ray free electron lasers to probe the dynamic motions of biological macromolecules. Currently we study visual rhodopsin, the core light sensing protein triggering the process of vision in humans.
  • X-ray crystallography: We routinely employ X-ray crystallography for probing the atomic scale 3D structures of biological macromolecules. We use high-throughput crystallization screening, optimization and X-ray diffraction at synchrotrons and XFELs.
  • XFEL Data Reduction and Analysis: We develop algorithms for data reduction of large data sets (>100 TB) generated by X-ray free electron lasers for both serial crystallography and solution scattering. We regularly provide data analysis support to dozens of research groups (internal and external to BioXFEL), including data reduction, analysis, modeling and interpretation.

Research Centers:

  • Center for Computational Research (CCR)

UB 2020 Strategic Strengths:

  • Molecular Recognition in Biological Systems and Bioinformatics

Grants and Sponsored Research:

  • March 2023–February 2028
    Mid-scale RI-2: Compact X-ray Free-Electron Laser Project
    National Science Foundation
    Role: Co-Investigator
    $91,000,000
  • October 2013–September 2025
    Biology with X-ray free electron lasers
    National Science Foundation
    Role: Co-Investigator
    $44,563,810
  • August 2019–July 2025
    High-resolution molecular recognition of ligands using solution X-ray scattering
    National Institutes of Health
    Role: Principal Investigator
    $1,333,637
  • June 2024–May 2025
    SWAXSFold: A New AI Tool to Determine Protein Structures
    Role: Principal Investigator
    $50,000
  • August 2018–July 2024
    Light-Induced Protein Quake of Visual Rhodopsin Investigated by Femtosecond Time-Resolved X-Ray Scattering
    National Science Foundation
    Role: Co-Principal Investigator
    $800,000
  • November 2019–October 2022
    Mid-scale RI-1 (M1:DP): Compact X-ray Free-Electron Laser Project
    National Science Foundation
    Role: Contributor
    $4,765,713
  • May 2020–May 2022
    RAPID: High-resolution structure determination of Coronavirus ligands by high-throughput WAXS
    National Science Foundation
    Role: Co-Principal Investigator
    $200,000
  • May 2020–July 2021
    MRI: Acquisition of a femtosecond laser system for time-resolved studies using CXLS
    National Science Foundation
    Role: Contributor
  • January 2025
    EmpireAI Alpha: SWAXSFold: Experiment-guided Structure Prediction for Drug Design
    Empire AI
    Role: Principal Investigator
    $512,409

Patents:

  • DENSS DENSS (DENsity from Solution Scattering) is open-source software developed for the reconstruction of 3D density from 1D solution scattering data. (2018)

Journal Articles:

  • Grant TD. (2018) Ab initio electron density determination directly from solution scattering data. Nat Methods (Mar), 15(3): 191-193.
  • Zuo X, Jussupow A, Ponomarenko NS, Grant TD, Tefft NM, Yadav NS, Range KL, Ralston CY, TerAvest MA, Sutter M, Kerfeld CA, Vermaas JV, Feig M, Tiede DM. (2025) Structure Characterization of Bacterial Microcompartment Shells via X-ray Scattering and Coordinate Modeling: Evidence for Adventitious Capture of Cytoplasmic Proteins. ACS applied bio materials (Mar), 8(3): 2090-2103.
  • Diandra Doppler, Alice Grieco, Domin Koh, Abhik Manna, Adil Ansari, Roberto Alvarez, Konstantinos Karpos, Hung Le, Mukul Sonker, Gihan K Ketawala, Samira Mahmud, Isabel Quereda Moraleda, Angel L Pey, Romain Letrun, Katerina Doerner, Jayanath CP Koliyadu, Raphael de Wijn, Johan Bielecki, Huijong Han, Chan Kim, Faisal HM Koua, Adam Round, Abhisakh Sarma, Tokushi Sato, Christina Schmidt, Mohammad Vakili, Dmitrii Zabelskii, Richard Bean, Adrian P Mancuso, Joachim Schulz, Raimund Fromme, Milagros Medina, Thomas D Grant, Petra Fromme, Richard A Kirian, Sabine Botha, Jose Manuel Martin-Garcia, Alexandra Ros. (2024) Minimized Sample Consumption for Time-Resolved Serial Crystallography Applied to the Redox Cycle of Human NQO1. bioRxiv (Apr)(2024.04.29.591466) doi:https://doi.org/10.1101/2024.04.29.591466
  • Chamberlain SR, Moore S, Grant TD. (2023) Fitting high-resolution electron density maps from atomic models to solution scattering data. Biophysical Journal (Dec), 122(39): 4567-4581. doi:10.1016/j.bpj.2023.10.034
  • Ishigami I, Carbajo S, Zatsepin N, Hikita M, Conrad CE, Nelson G, Coe J, Basu S, Grant T, Seaberg MH, Sierra RG, Hunter MS, Fromme P, Fromme R, Rousseau DL, Yeh SR. (2023) Detection of a Geminate Photoproduct of Bovine Cytochrome c Oxidase by Time-Resolved Serial Femtosecond Crystallography. J Am Chem Soc (Oct), 145(41): 22305-22309. doi:10.1021/jacs.3c07803
  • Zielinski KA, Sui S, Pabit SA, Rivera DA, Wang T, Hu Q, Kashipathy MM, Lisova S, Schaffer CB, Mariani V, Hunter MS, Kupitz C, Moss FR 3rd, Poitevin FP, Grant TD, Pollack L. (2023) RNA structures and dynamics with Å resolution revealed by x-ray free electron lasers. Science Advances (Sep), 9(39) doi:10.1126/sciadv.adj3509
  • Doppler D, Sonker M, Egatz-Gomez A, Grieco A, Zaare S, Jernigan R, Meza-Aguilar JD, Rabbani MT, Manna A, Alvarez RC, Karpos K, Cruz Villarreal J, Nelson G, Yang JH, Carrion J, Morin K, Ketawala GK, Pey AL, Ruiz-Fresneda MA, Pacheco-Garcia JL, Hermoso JA, Nazari R, Sierra R, Hunter MS, Batyuk A, Kupitz CJ, Sublett RE, Lisova S, Mariani V, Boutet S, Fromme R, Grant TD, Botha S, Fromme P, Kirian RA, Martin-Garcia JM, Ros A. (2023) Modular droplet injector for sample conservation providing new structural insight for the conformational heterogeneity in the disease-associated NQO1 enzyme. Lab on a Chip (Jun), 23(13): 3016-3033. doi:10.1039/d3lc00176h
  • Jernigan RJ, Logeswaran D, Doppler D, Nagaratnam N, Sonker M, Yang JH, Ketawala G, Martin-Garcia JM, Shelby ML, Grant TD, Mariani V, Tolstikova A, Sheikh MZ, Yung MC, Coleman MA, Zaare S, Kaschner EK, Rabbani MT, Nazari R, Zacks MA, Hayes B, Sierra RG, Hunter MS, Lisova S, Batyuk A, Kupitz C, Boutet S, Hansen DT, Kirian RA, Schmidt M, Fromme R, Frank M, Ros A, Chen JJ, Botha S, Fromme P. (2023) Room-temperature structural studies of SARS-CoV-2 protein NendoU with an X-ray free-electron laser. Structure (London, England : 1993) (Feb), 31(2): 138-151.e5. doi:10.1016/j.str.2022.12.009
  • Grant TD. (2023) Reconstruction of 3D density from solution scattering. Methods in enzymology (Jan), 678: 145-192.
  • Sonker M, Doppler D, Egatz-Gomez A, Zaare S, Rabbani MT, Manna A, Cruz Villarreal J, Nelson G, Ketawala GK, Karpos K, Alvarez RC, Nazari R, Thifault D, Jernigan R, Oberthür D, Han H, Sierra R, Hunter MS, Batyuk A, Kupitz CJ, Sublett RE, Poitevin F, Lisova S, Mariani V, Tolstikova A, Boutet S, Messerschmidt M, Meza-Aguilar JD, Fromme R, Martin-Garcia JM, Botha S, Fromme P, Grant TD, Kirian RA, Ros A. (2022) Electrically stimulated droplet injector for reduced sample consumption in serial crystallography. Biophysical reports (Dec), 2(4): 100081. doi:10.1016/j.bpr.2022.100081
See all (34 more)

Books and Book Chapters:

  • Thomas D. Grant. (2022) Reconstruction of 3D density from solution scattering. In: Methods in Enzymology: Scattering Methods for Biological Macromolecules. Elsevier; Academic Press
  • Eaton E Lattman, Thomas D Grant, Edward H Snell. (2018) Biological Small Angle Scattering: Theory and Practice. Oxford University Press.

Abstracts:

  • Thomas D. Grant, Sarah R. Chamberlain, Jitendra Singh, Patrick Oduro. (2024) High-resolution structure determination of protein-ligand complexes using solution scattering. American Crystallographic Association: SAS in Biotherapeutics & Drug Development. Denver, ColoradoUnited States (Jul) Oral
  • Thomas D. Grant. (2022) Using DENSS for ab initio 3D density reconstructions from SAXS data. John Spence Memorial Symposium. Tempe, ArizonaUnited States (Oct) Poster; Oral
  • Stephen Moore, Thomas D Grant. (2022) New algorithms for interpreting time-resolved SAXS. 72nd American Crystallographic Association Annual Meeting. Portland, OregonUnited States (Jul) Oral
  • Thomas D Grant. (2020) Ab initio electron density determination directly from solution scattering data. 2020 SSRL/LCLS Users’ Meeting. Virtual, (Oct) Poster
  • Thomas D Grant, et. al. (2020) Ultrafast membrane protein dynamics revealed by X-ray scattering with a femtosecond free-electron laser. Biophysical Society 2021 Annual Meeting. Virtual, (Oct) Poster
  • Thomas D Grant. (2020) Ab initio electron density determination directly from solution scattering data. 64th Annual Biophysical Society Meeting. San Diego, CaliforniaUnited States (Feb) Oral
  • Thomas D Grant. (2019) Ab initio electron density determination directly from solution scattering data. Nature Conference: Functional Dynamics – Visualizing Molecules in Action. Tempe, ArizonaUnited States (Nov) Poster
  • Thomas D Grant. (2019) Ab initio electron density determination directly from solution scattering data. 2019 Meeting of the American Crystallographic Association. Covington, KentuckyUnited States (Jul) Poster
  • Thomas D Grant. (2019) Solving the phase problem in solution scattering. 6th Annual BioXFEL International Conference. San Diego, CaliforniaUnited States (May) Poster
  • Thomas D Grant. (2019) Solving the phase problem in solution scattering. BioXFEL Annual NSF Site Visit. Buffalo, New YorkUnited States (May) Poster
See all (23 more)

Professional Memberships:

  • Biophysical Society (2019–present)
  • American Association for the Advancement of Science (2014–present)
  • American Crystallographic Association (2008–present)

Presentations:

  • "Advanced SAXS data analysis: 3D reconstructions and fitting" Everything BioSAXS 10 Workshop (2024)
  • "High-resolution structures of protein-ligand complexes using solution scattering" University of Arizona Physical and Analytical Chemistry Guest Seminar (2024)
  • "High-resolution structures of protein-ligand complexes from solution scattering" SLAC Users Meeting, SLAC National Accelerator Laboratory (2024)
  • "Ab initio reconstruction of shape from scattering data" BioSAXS Workshop at the 2024 American Crystallographic Association Meeting (2024)
  • "Advanced SAXS data analysis: 3D reconstructions and fitting" BioSAXS Workshop at the 2024 American Crystallographic Association Meeting (2024)
  • "My career path to academia" Science Careers Perspectives Panel (BioXFEL Summer Intern Program) (2024)
  • "Introduction to XFELs" BioXFEL Summer Student Orientation (2024)
  • "Solution Scattering at XFELs" BioXFEL Summer Student Seminar (2024)
  • "High-resolution structure determination of protein-ligand complexes using solution scattering" BioXFEL Spring Symposium (2024)
  • "High-resolution structures of protein-drug complexes with solution scattering" University of Rochester Guest Seminar Speaker (2023)
See all (79 more)

Service Activities:

  • Committee to review Presidential and Schomburg Fellowship distributions to each of the decanal units at UB through the Graduate School. These prestigious awards help to recruit the highest level students to UB’s graduate programs.; Member of UB Graduate Fellowship Committee (2025)
  • Seminar Committee, Department of Structural Biology; Co-Chair (2025–present)
  • Careers in STEM Panel for BioXFEL Summer Interns; Panel Member (2024)
  • SSRL Synchrotron BIO Proposal Review Panel, Reviewing X-ray beamtime proposals four times per year, each ~12 total hours contribution.; Panel Member (2024–2028)
  • NIH MSFC Study Section; Panel Member (2024)
  • Session Chair: Biomolecular Dynamics and Frontiers in SAS Session, 2024 Annual Meeting of the ACA; Session Chair (2024)
  • Faculty Search Committee Member; Faculty Search Committee Member (2023–2024)
  • PNAS Nexus; Referee (2023–present)
  • Careers in STEM for Graduate Students and Postdocs (BioXFEL); Panel Member (2023)
  • Faculty Search Committee; Faculty Search Committee (2022–2023)
  • Committee to review Presidential and Schomburg Fellowship distributions to each of the decanal units at UB through the Graduate School. These prestigious awards help to recruit the highest level students to UB’s graduate programs.; Member of UB Graduate Fellowship Committee (2022)
  • Session Chair: Time-resolved Structural Dynamics at the 2022 ACA Annual Conference; Session Chair (2022)
  • BioXFEL Summer Internship Orientation Lecturer; Guest Lecturer (2022)
  • Peer-reviewer for Structural Dynamics; Reviewer (2022–present)
  • Committee member for Jitendra Singh, PhD student; Graduate Student Committee Member (2022)
  • Novo Nordisk Foundation; Research Infrastructure: Large Equipment and Facilities in Biomedicine and;; Grant Reviewer (2022)
  • Jacobs School Research Growth Opportunities discussion; Member (2022)
  • Committee member for Fardin Ahmed, PhD student; Graduate Student Committee Member (2022)
  • Chair: Small Angle Scattering Special Interest Group of the American Crystallographic Association; Chair (2022)
  • Committee member for Monica MacDonald, PhD student.; Graduate Student Committee Member (2022)
  • Committee member for Stephen Moore, PhD student; Graduate Student Committee Member (2021–2022)
  • Chair of Nucleic Acid Structure and Function session of the 3rd International Conference on Nucleic Acids and CRISPR; Session Chair (2021)
  • Chair for 9th BioXFEL International Conference; Conference Chair (2021–2022)
  • Committee member for Nicholas Clark, PhD student; Graduate Student Committee Member (2021–2022)
  • Chair: Small Angle Scattering Special Interest Group, American Crystallographic Association; Chair (2020–present)
  • IUCrJ Journal Referee; Peer Reviewer (2020–present)
  • PPBS Admissions Committee. Review all PPBS applicants, discuss in committee, and select candidates.; Member (2020–2024)
  • Session Chair: Frontiers in SAS, 2020 Meeting of the American Crystallographic Association; Session Chair (2020)
  • BioXFEL Summer Internship Orientation Lecturer; Guest Lecturer (2020)
  • Physical Review Applied Journal Referee; Peer Reviewer (2019–present)
  • Novo Nordisk Foundation; Research Infrastructure: Large Equipment and Facilities in Biomedicine and;; Grant Reviewer (2019)
  • BioXFEL Summer Internship Orientation Lecturer; Guest Lecturer (2019)
  • NSF; NSF MRI 2; Major Research Instrumentation;; Panel Member (2019)
  • Structural Dynamics Journal Referee; Peer Reviewer (2019–present)
  • Acta Crystallographica Section D: Structural Biology Journal Referee; Peer Reviewer (2019–present)
  • Session Chair: Biomolecular Methods II, SAS2018 International Small Angle Scattering Conference; Chair (2018)
  • Faculty Council; Member (2018–present)
  • BioXFEL Summer Internship Orientation Lecturer; Guest Lecturer (2018)
  • BioXFEL 6th International Conference Organizing Committee Selecting speakers, designing agenda, etc for the 2019 BioXFEL Conference.; Organizing Committee Member (2018–2019)
  • Nature Scientific Reports Journal Referee; Peer Reviewer (2018–present)
  • New Opportunities at the European XFEL Workshop Organizer; Co-Chair (2018)
  • BioXFEL Summer Internship Orientation Lecturer; Guest Lecturer (2017)
  • Serial Crystallography Data Analysis Workshop Organizer and Lecturer; Co-Chair (2016)
  • BioXFEL Summer Internship Orientation Lecturer; Guest Lecturer (2016)
  • Session Chair: Beyond Crystals II, BioXFEL 3rd Annual Conference; Chair (2016)
  • BioXFEL Annual Meeting Poster Blitz Organizer; Chair (2016–present)
  • BioXFEL Annual Conference Poster Judge; Judge (2016–present)
  • Journal of Applied Crystallography Referee; Peer Reviewer (2016–present)
  • Serial Crystallography Data Analysis Workshop Organizer and Lecturer; Co-Chair (2015)
  • BioXFEL Summer Internship Orientation Lecturer; Guest Lecturer (2015)
  • BioXFEL Knowledge Transfer. I write the annual Knowledge Transfer report for the BioXFEL STC led by UB. I present the Knowledge and Technology Transfer efforts to the annual NSF Site Review committee. This includes all scientific publications and presentations by BioXFEL members in all 8 institutions, collecting all information on patents among member institutions supported by BioXFEL research, collecting all information on public and government-related activities for the Center.; Member (2015–present)
  • BMC Structural Biology Journal Referee; Peer Reviewer (2015–present)
  • CHESS Beamtime Proposal Reviewer; Reviewer (2015–present)
  • Serial Crystallography Data Analysis Workshop Organizer and Lecturer; Co-Chair (2014)
  • BioXFEL Summer Internship Orientation Lecturer; Guest Lecturer (2014)
  • BioXFEL Education and Diversity Committee This committee governs all aspects of the education and diversity programs in the BioXFEL Center.; Member (2014–present)
  • BioXFEL Education and Diversity Committee. Create educational programs for BioXFEL (NSF STC led by UB) students, postdocs and young scientists. Design and implement diversity initiatives in BioXFEL for all member institutions including significant efforts with the University at Puerto Rico campuses, and HBCUs.; Member (2014–present)

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Contact Information

955 Main Street
Room 5156
Buffalo, New York 14203
Phone: 716-829-5490
tdgrant@buffalo.edu