This proposal seeks funding to support and extend an interdisciplinary predoctoral program that prepares students with strong backgrounds in quantitative physical sciences to conceptualize, conduct, and direct independent research in molecular biophysics and structural biology. This Molecular Biophysics and Structural Biology (MBSB) program places a strong emphasis on interdisciplinary, collaborative research in an environment where the practical human health consequences of research are appreciated and contribute to guiding and driving basic research. The training faculty consists of 40 independent investigators spread over 14 departments within the School of Medicine and the Faculty of Arts and Sciences at the University of Pittsburgh and within Carnegie Mellon University. The training faculty comprises a large group of senior members who have strong records in graduate training, funding, and publication, and a smaller contingent of junior faculty who bring new ideas and technical expertise to the group. The research programs of training faculty emphasize not only characterization of biomolecular phenomena but also development of new methodologies. At every stage of the curriculum, emphasis is placed on the relationship between physical methods and biological understanding. The research is concentrated in core areas at the challenging forefront of biomolecular science, including membrane proteins, protein-protein interactions and oligomeric complexes, nucleic acid structure and protein-nucleic acid interactions, poorly structured protein elements, protein misfolding and aggregation, and small molecule ligand - protein interactions. The training program includes a first year core curriculum featuring an introduction to biophysical instrumentation and methods, how these are used to address specific molecular questions, an introduction to theory and simulation of biomolecular behavior, and courses on statistical analysis and computer programming. Student's abilities to synthesize and creatively utilize what they have learned in the classroom are tested in a qualifying exam that requires them to construct and defend a research proposal not related to their own laboratory work. After passing this exam students move on to develop and pursue their thesis project. Students are required to participate in a weekly journal/data club and to attend a Molecular Biophysics seminar series featuring invited local and national speakers. Students are also encouraged to participate in several local, annual science meetings. This application proposes special features new to the MBSB program including incentives to develop co-mentored, collaborative thesis projects and an annual mini-symposium, with significant student participation, set within the MBSB graduate program. Students are also encouraged to take advantage of the rich environment of the School of Medicine to attend seminars in molecular aspects of human disease. We are requesting funds to support six traineeships with the goal to train a new generation of molecular biophysicists who will be leaders in future efforts to understand normal and abnormal human biology at the physical and molecular level.

Public Health Relevance

Future progress in the understanding and treatment of many diseases will require a thorough knowledge of the molecular and biophysical processes underlying normal and abnormal biology. This application proposes to support and strengthen a growing multi-disciplinary, multi-departmental graduate program in Molecular Biophysics and Structural Biology which will train students to conduct physical and molecular research in a medical school environment where collaborative, health related projects are encouraged.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Institutional National Research Service Award (T32)
Project #
5T32GM088119-03
Application #
8501540
Study Section
National Institute of General Medical Sciences Initial Review Group (BRT)
Program Officer
Flicker, Paula F
Project Start
2011-07-01
Project End
2016-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2013
Total Cost
$178,618
Indirect Cost
$8,490
Name
University of Pittsburgh
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Boatz, Jennifer C; Whitley, Matthew J; Li, Mingyue et al. (2017) Cataract-associated P23T ?D-crystallin retains a native-like fold in amorphous-looking aggregates formed at physiological pH. Nat Commun 8:15137
Lin, Hsiang-Kai; Boatz, Jennifer C; Krabbendam, Inge E et al. (2017) Fibril polymorphism affects immobilized non-amyloid flanking domains of huntingtin exon1 rather than its polyglutamine core. Nat Commun 8:15462
Mandal, Abhishek; Boatz, Jennifer C; Wheeler, Travis B et al. (2017) On the use of ultracentrifugal devices for routine sample preparation in biomolecular magic-angle-spinning NMR. J Biomol NMR 67:165-178
Punihaole, David; Jakubek, Ryan S; Workman, Riley J et al. (2017) Monomeric Polyglutamine Structures That Evolve into Fibrils. J Phys Chem B 121:5953-5967
Kong, Muwen; Beckwitt, Emily C; Springall, Luke et al. (2017) Single-Molecule Methods for Nucleotide Excision Repair: Building a System to Watch Repair in Real Time. Methods Enzymol 592:213-257
Eells, Rebecca; Barros, Marilia; Scott, Kerry M et al. (2017) Structural characterization of membrane-bound human immunodeficiency virus-1 Gag matrix with neutron reflectometry. Biointerphases 12:02D408
Kar, Karunakar; Baker, Matthew A; Lengyel, George A et al. (2017) Backbone Engineering within a Latent ?-Hairpin Structure to Design Inhibitors of Polyglutamine Amyloid Formation. J Mol Biol 429:308-323
Merg, Andrea D; Boatz, Jennifer C; Mandal, Abhishek et al. (2016) Peptide-Directed Assembly of Single-Helical Gold Nanoparticle Superstructures Exhibiting Intense Chiroptical Activity. J Am Chem Soc :
Debiec, Karl T; Cerutti, David S; Baker, Lewis R et al. (2016) Further along the Road Less Traveled: AMBER ff15ipq, an Original Protein Force Field Built on a Self-Consistent Physical Model. J Chem Theory Comput 12:3926-47
Hoop, Cody L; Lin, Hsiang-Kai; Kar, Karunakar et al. (2016) Huntingtin exon 1 fibrils feature an interdigitated ?-hairpin-based polyglutamine core. Proc Natl Acad Sci U S A 113:1546-51

Showing the most recent 10 out of 30 publications