Department website: http://biophysics.jhu.edu/
The Department of Biophysics offers programs leading to the B.A., M.S., and Ph.D. degrees. Biophysics is appropriate for students who wish to develop and integrate their interests in the physical and biological sciences, and is an excellent major for students interested in medical school, for students interested in graduate studies in the molecular biosciences, and for students interested in positions in biotechnology and the pharmaceutical industry. The small class size and emphasis on classroom instruction by tenure track faculty provides a close-knit environment where undergraduate biophysics majors develop close and lasting relationships with their professors.
Research interests in the Department cover experimental and computational biophysics, with topics that address the function and biology of molecular and cellular structures, membrane organization, biomolecular energetics, and macromolecular physical chemistry. The emphasis on independent research in faculty labs bring undergraduate as well as graduate students in contact with biophysical scientists throughout the university. Regardless of their choice of research area, students are exposed to a wide range of problems of biological interest. For more information, and for the most up-to-date list of course offerings and requirements, consult the department web page.
Research Activities of Primary Faculty
Protein Engineering and Biophysics (Dr. Garcia-Moreno)
To understand how biological macromolecules work and to design and engineer new macromolecules, it is important to understand in detail the relationship between structure and energetics. We study this problem in our lab by analysis of the connection between structure, thermodynamic stability, and dynamics of proteins with a combination of computational and experimental methods. Our research depends heavily on the application of NMR spectroscopy, X-ray crystallography, and equilibrium thermodynamics. These experimental methods contribute the physical insight needed to develop computational methods for structure-based energy calculations, and generate the data required to benchmark these methods. We are focused on problems of protein electrostatics because electrostatic energy is the most useful metric for correlating structure with function in all the most important energy transduction processes in biological systems. We focus on the engineering of proteins with pH sensing.
Biophysics of RNA (Dr. Woodson)
The control of cell growth and type depends on the ability of RNA to fold into complex three-dimensional structures. RNA catalysts are good models for studying the physical principles of RNA folding, and the assembly of protein-RNA complexes such as the ribosome. Changes in RNA three-dimensional structure are monitored by fluorescence spectroscopy, “X-ray footprinting,” and neutron scattering. Bacterial and yeast expression systems are used to study intracellular folding of RNA.
Protein Folding and Design, Notch Signaling (Dr. Barrick)
The folding of proteins into their complex native structures is critical for proper function in biological systems. This spontaneous process of self-assembly is directed by physical chemistry, although the rules are not understood. We use repeat-proteins, linear proteins with simple architectures, to dissect the energy distribution, sequence-stability relationships, and kinetic routes for folding. We are also using consensus sequence design to explore how sequence statistics represented in multiple sequence alignments can be used to engineer protein stability, structure, and function in globular proteins. In addition, we are studying the molecular mechanisms of Notch signaling, a eukaryotic transmembrane signal transduction pathway important for human development and disease. The transmission of information across the membranes of cells is essential for cell differentiation and homeostasis; signaling errors result in disease states including cancer. We are focusing on interactions between proteins involved in Notch signaling using modern biophysical methods. Thermodynamics of association and allosteric effects are determined by spectroscopic, ultracentrifugation, and calorimetric methods. Atomic structure information is being obtained by NMR spectroscopy.
NMR Spectroscopy (Dr. Lecomte)
Many proteins require stable association with an organic compound for proper functioning. One example of such “cofactor” is the heme group, a versatile iron-containing molecule capable of catalyzing a broad range of chemical reactions. The reactivity of the heme group is precisely controlled by interactions with contacting amino acids. Structural fluctuations within the protein are also essential to the fine-tuning of the chemistry. We are studying how the primary structure of cytochromes and hemoglobins codes for heme binding and the motions that facilitate function. Our method of choice is nuclear magnetic resonance spectroscopy, which we use to obtain detailed structural and dynamic representations of proteins with and without bound heme. Our ultimate goal is to understand the evolution of chemical properties in heme proteins and how to alter them.
Structural and Energetic Principles of Membrane Proteins (Dr. K. Fleming)
Membrane proteins must fold to unique native conformations and must interact in specific ways to form complexes essential for life. Currently, the chemical principles underlying these processes are poorly understood. Thermodynamic and kinetic studies on membrane proteins with diverse folds and oligomeric states are carried out with the goal of discovering the physical basis of stability and specificity for membrane proteins. Our research results in a quantitative understanding of sequence-structure-function relationships that can ultimately be used to describe membrane protein populations in both normal and disease states, to design novel membrane proteins, and to develop therapeutics that modulate membrane protein functions in desirable ways.
Chromatin Remodeling (Dr. Bowman)
Chromatin, the physical packaging of eukaryotic chromosomes, plays a major role in determining the patterns of gene silencing and expression across the genome. Chromatin remodelers are multicomponent protein machines that establish and maintain various chromatin environments through the assembly, movement, and eviction of nucleosomes. At present, the molecular mechanisms by which chromatin remodelers alter chromatin structure are not understood. Our long-term goal is to gain a molecular understanding of the remodeling process and in particular how remodeling is coupled to the transcriptional machinery. Our strategy is to couple structure determination with functional studies to determine how different components of a chromatin remodeler cooperate and interact with the nucleosome substrate.
Theoretical Biophysics (Dr. Johnson)
Protein interaction networks capture the cooperation required by proteins to carry out complex functions in the cell. The ability of proteins to assemble to form transient or permanent complexes and transmit signals or nutrients depends on their concentrations, their binding partners, and their spatial and temporal dynamics in the cell. Using computation and theory, we are building models to accurately simulate these multi-protein assembly processes, such as those occurring in endocytosis, that are critical to cell survival. We complement these detailed simulations with coarse-grained models to extend to larger protein interaction networks and characterize the role of network topology on protein binding specificity and dynamics.
Cellular Physics (Dr. Camley)
Biophysics Theory and Modeling (Dr. Zhang)
metabolism, signaling, and more. Unlike conventional phase separation, e.g., the demixing of oil and water, the underlying interactions that drive biomolecular phase separation are complex, typically involving both specific and non-specific interactions and often among multiple components. These interactions are regulated by the cell in ways that allow condensates to carry out specific biological functions, yet the complexity of these interactions poses challenges to understanding how the microscopic features of biomolecules lead to the macroscopic properties and functions of condensates. We utilize physical, mathematical, and computational tools and work closely with experimental groups to understand such emergent connections. In addition, we are broadly interested in the complex behaviors of biomolecules and their assemblies across scales, from RNA folding and DNA bending, to macromolecular transport through nuclear pore complexes and intracellular space, to genome organization.
Structure and Mechanism of How Cells Read and Repair the Genome (Dr. He)
Biochemical Reactions on Cell Membranes (Dr. Huang)
The cell membrane hosts a myriad of biochemical reactions critical to cellular functions. The coupling of reactions with a physical surface enables a rich array of unique mechanisms in space and time that are rarely encountered in solution biochemistry. We explore this theme in the case of signal transduction, the process by which chemical information is integrated in living cells. The research approach combines optical methods, including single-molecule imaging and spectroscopy, and kinetic modeling to analyze biochemically reconstituted systems and living cells. The natural integration between physical methods, biochemistry, and cell biology stimulates the invention of imaging assays that advance the degree to which complex signaling processes can be resolved in real time. With the advent of quantitative descriptions of signal transduction, the overarching goal is to formulate a physical understanding of biochemical reactions in living systems.
Facilities
The Department of Biophysics shares state-of-the-art equipment for X-ray diffraction analysis, NMR spectroscopy, solution biophysical studies, and numerically intensive computer simulations with other biophysics units and departments within the University. In addition, the department houses a full complement of equipment for molecular biological and biochemical work, and for various kinds of spectroscopy, calorimetry, and hydrodynamic studies.
Undergraduate Program
The undergraduate major in biophysics is intended for the student interested in advanced study of biophysics or the related fields of biochemistry, quantitative or computational biology, molecular biology, physiology, pharmacology, and neurobiology. The biophysics major fulfills all typical science premedical requirements with the exception of Organic Chemistry Lab (AS.030.225 Introductory Organic Chemistry Laboratory or AS.030.227 Chemical Chirality: An Introduction in Organic Chem. Lab, Techniques). The student majoring in biophysics, with the advice of a member of the department, chooses a program of study that will include foundation courses in biology, chemistry, and physics followed by advanced studies in biophysics, and independent research. The biophysics major requires that students earn a grade of “C” or greater for all courses required in the major. A student who earns a grade of “C-“ or below must repeat the course and earn a better grade.
For additional information on academic requirements and department events for majors, check the undergraduate website.
Doctoral Programs
The Thomas C. Jenkins Department of Biophysics trains students in two Ph.D. programs, the Jenkins Biophysics Program and the Program in Molecular Biophysics. The annual application deadline for both programs is typically December 1.
Financial Aid
Two National Institutes of Health training grants currently provide stipend and tuition support: one is for students who enroll in PMB and the other is for those who enter CMDB. Students supported by these training grants must be U.S. citizens or permanent residents. In addition, several research assistantships funded by grants and contracts awarded to faculty by outside agencies may be available to qualified students.
University fellowships providing remission of tuition are also available. Graduate students in biophysics are eligible for and encouraged to apply for various nationally administered fellowships, such as National Science Foundation fellowships.
The Jenkins graduate program is open to all students including international students. Students in this program are supported, in part, through TA-ships.
It is anticipated that financial support covering normal living costs and tuition will be made available to accepted students.
For current course information and registration go to https://sis.jhu.edu/classes/