Professor Bowman received his undergraduate degree from the University of North Carolina at Chapel Hill and carried out his Ph.D. work at Princeton University. In the laboratory of C.E. Schutt, Dr. Bowman focused on X-ray crystallography, studying actin-binding proteins and an enterotoxin from rotavirus. He continued a focus on structural biology as a postdoc in the laboratory of John Kuriyan at UC Berkeley, where his structure of the pentameric RFC clamp loader bound to the trimeric PCNA sliding clamp suggested how DNA stimulated ATP hydrolysis and release of the clamp. He joined the faculty of the Biophysics Department at Johns Hopkins in 2005, where his group’s focus has been on the structure and mechanisms of chromatin remodelers.
In many organisms, including humans, DNA is packaged up into thousands (to millions) of tiny cylindrical structures called nucleosomes. Nucleosomes, which consist of a histone core tightly wrapped by ~146 base pairs of duplex DNA, restrict access to DNA, and therefore must be reorganized to allow access to the underlying DNA sequence. Many cellular factors participate in the assembly and disassembly of nucleosomes, and disruptions of many chromatin-regulating factors have been linked to a number of human diseases, notably cancer.
We study a class of motor proteins, called chromatin remodelers, that actively reorganize nucleosomes. Chromatin remodelers are helicase-type motors that use the energy of ATP hydrolysis to translocate along DNA. Our overall goals are to understand both how chromatin remodelers work and how they are regulated. Chromatin remodelers have a number of functionally important domains that appear to communicate with the core ATPase motor. We and others are just beginning to understand how the non-ATPase domains guide action of the remodeler toward specific nucleosome substrates, or to produce a specific remodeling outcome.
Introduction to Computing (250.649)
(Bowman, Barrick, Garcia-Moreno, Lau)
This class, referred to as “computer bootcamp,” gives students hands-on experience in scripting with Unix, Python, and Mathematica. It is geared toward first-year graduate students, and no prior programming experience is required. The goal is for the students to become computationally independent: that is, to be able to ask their own questions through script writing rather than being limited by existing computer programs. Classes are presented as interactive computer labs, where students are given time to work through exercises in class, with short lectures and some group discussion to help those less familiar with programming.
Proteins and Nucleic Acids (250.685)
The goal of this course is to introduce some fundamental aspects of protein and nucleic acid structure/function/energetics, using papers from the primary literature. This course is intended for first year graduate students, and each class consists of a 15- to 30-minute lecture, followed by a discussion of assigned papers. Students are expected to be able to explain experimental design, the results, and implications of the studies. An overall goal of the course is for students to gain experience and confidence in reading and evaluating scientific papers. To additionally stimulate students to clearly and concisely explain scientific ideas and data, late in the semester each member of the class presents a short talk on a topic not covered in class. Another component of the class are weekly problem sets (on assigned reading), which also present a python programming problem based on a molecular structure. Students without prior programming experience are expected to take Introduction to Computing (250.649).
Methods in Molecular Biophysics (250.690)
(Barrick, Bowman, Lecomte, Fleming, Xiao, Ha)
This first year graduate course presents fundamental methods in biophysics, including fluorescence spectroscopy, X-ray crystallography, NMR, analytical ultracentrifugation, and single-molecule methods. The course is primarily lecture-based, with weekly problem sets that reinforce the material for each section.
Advanced Seminars in Structural Biology of Chromatin (250.411)
This is an upper-level undergraduate course that is based heavily on assigned papers from the primary literature. Each class is centered around a structure or class of structures involved in transcriptional regulation (e.g. the nucleosome, RNA polymerase, RNAi machinery, helicases). To prepare for each class, the students are given an assignment where they must use the Pymol graphics program to visualize and answer questions about macromolecular structures. In class, I use Pymol to illustrate structural concepts and lead a seminar-style discussion through several scientific papers. At the end of the semester, each student writes a 20-page paper and gives a class presentation on a new topic not covered in the course. Overall, this class is designed to not only give students an in-depth understanding of several key topics in the transcriptional field, but help them transition to a graduate-level ability of reading and extracting information from scientific papers.
Nodelman I.M., Bleichert F., Patel A., Ren R., Horvath K.C., Berger J.M., Bowman G.D. (2017) Interdomain communication of the Chd1 chromatin remodeler across the DNA gyres of the nucleosome. Mol Cell. Jan 17, 2017. DOI: 10.1016/j.molcel.2016.12.011
Levendosky R.F., Sabantsev A., Deindl S., Bowman G.D. (2016) The Chd1 chromatin remodeler shifts hexasomes unidirectionally. eLife 2016;10.7554/eLife.21356.
Nodelman I.M., Horvath K.C., Levendosky R.F., Winger J., Ren R., Patel A., Li M., Wang M.D., Roberts E., Bowman G.D. (2016) The Chd1 chromatin remodeler can sense both entry and exit sides of the nucleosome. Nucleic Acids Res. Sep 19;44(16):7580-91.
McKnight J.N., Tsukiyama T., Bowman G.D. (2016) Sequence-targeted nucleosome sliding in vivo by a hybrid Chd1 chromatin remodeler. Genome Res. doi: 10.1101/gr.199919.115
Li M., Hada A., Sen P., Olufemi L., Hall M.A., Smith B.Y., Forth S., McKnight J.N., Patel A., Bowman G.D., Bartholomew B., Wang M.D. (2015) Dynamic regulation of transcription factors by nucleosome remodeling. Elife. Jun 5;4.
Bowman, G.D., Porier, M.G. (2015) Post-Translational Modifications of Histones that Influence Nucleosome Dynamics. Chem Rev. 115(6):2274-95.
Nodelman, I.M., Bowman, G.D. (2013) Nucleosome sliding by Chd1 does not require rigid coupling between DNA-binding and ATPase domains. EMBO Reports, 14(12):1098-103.
Torigoe, S.E., Patel, A., Khuong, M.T., Bowman, G.D., Kadonaga, J.T. (2013) ATP-dependent Chromatin Assembly Is Functionally Distinct from Chromatin Remodeling. eLife 2013;2:e00863.
Patel, A., Chakravarthy, S., Morrone, S., Nodelman, I.M., McKnight, J.N., Bowman, G.D. (2013) Decoupling nucleosome recognition from DNA binding dramatically alters the properties of the Chd1 chromatin remodeler. Nucleic Acid Res. 41(3):1637-48.
Sharma, A., Jenkins, K.R., Héroux, A., Bowman, G.D. (2011) Crystal Structure of the Chromodomain Helicase DNA-Binding Protein 1 (Chd1) DNA-Binding Domain in Complex with DNA. J Biol Chem. 286 (49):42099-104.
Patel, A., McKnight, J.N., Genzor, P., Bowman, G.D. (2011) Identification of Residues in Chromodomain Helicase DNA-Binding Protein 1 (Chd1) Required for Coupling ATP Hydrolysis to Nucleosome Sliding. J Biol Chem. 286 (51):43984-93.
Hauk, G,. Bowman, G.D. (2011) Structural Insights into Regulation and Action of SWI2/SNF2 ATPases. Curr Opin Struct Biol. 21(6):719-27.
McKnight J.N., Jenkins, K.R., Nodelman I.M., Escobar T., Bowman, G.D. (2011) Extranucleosomal DNA Binding Directs Nucleosome Sliding By Chd1. Mol. Cell Biol. 31(23):4746-59.
Hauk*, G,. McKnight*, J., Nodelman, I.M., Bowman, G.D. (2010) The Chromodomains of the Chd1 Chromatin Remodeler Regulate DNA Access to the ATPase Motor. Mol Cell. 39(5):711-23. (* equal contribution)
Sczepanski, J.T., Wong, R.S., McKnight, J.N., Bowman, G.D., Greenberg, M.M. (2010) Rapid DNA-protein cross-linking and strand scission by an abasic site in a nucleosome core particle. Proc Natl Acad Sci U S A. 107(52):22475-80.
Bowman, G.D. (2010) Mechanisms of ATP-dependent nucleosome sliding. Curr. Opin. Struct. Biol. 20:73-81.
Celedon, A., I.M. Nodelman, B. Wildt, R. Dewan, P. Searson, D. Wirtz, G.D. Bowman, and S.X. Sun. (2009) Magnetic tweezers measurement of single molecule torque. Nano Lett. 9:1720-1725.