Doctor of Philosophy
Students with outstanding academic records who have been accepted into the MD program may apply for admission to a combined degree program leading to the MS and MD or to the PhD and MD degrees. Completion of the dual-degree program usually requires a minimum of seven years.
Program Admissions Requirements
In addition to the general Graduate School admission requirements, this program has additional specific requirements.
The Biophysics Graduate Program encourages applications from students with a strong background in chemistry, biology, biochemistry, physics or mathematics and an enthusiasm for carrying out scientific research. The Program consists of two major and largely independent sections—Molecular Biophysics and Magnetic Resonance Imaging. The Molecular Biophysics section is a component member of the Interdisciplinary Program in Biomedical Sciences (IDP) and students wishing to pursue this track should apply to the IDP. The faculty in this section use biophysical techniques to study free radicals and paramagnetic metal ions in biological systems. For example, current research includes studies on protein structure, functional dynamics, and free radical spin trapping. The Magnetic Resonance Imaging section emphasizes research in the areas of cognitive neuroscience, signal processing, statistical analysis, image production, and hardware development. Applicants to this track are expected to have a high level of competence in physics and mathematics.
Fields of Research
Studies of metallo anti-tumor agents; adducts and dynamics of copper complexes; EPR of mixed valence centers in proteins. (Dr. Antholine)
Transition metal-containing enzymes and electron-transfer proteins: the roles of transition ion catalytic and redox-active centers in life-threatening conditions. (Dr. Bennett)
Mapping of human brain language systems with magnetic resonance imaging. (Dr. Binder)
Mapping of activity in human brain visual systems with magnetic resonance imaging. (Dr. DeYoe)
Site directed mutagenesis; structure-function relationships for membrane proteins; protein folding and dynamics. Antibiotic peptides. (Dr. Feix)
Mathematical modeling and simulation of complex biological systems. (Dr. Greene)
Biological chemistry of nitric oxide and related species in physiology and pathology. Oxidative biology of Sickle Cell disease. (Dr. Hogg)
Mechanism of anesthesia with respect to loss and return of consciousness as studied by electrophysiological and brain imaging methods. (Dr. Hudetz)
Electron spin resonance instrumentation and physics; oxygen transport and uptake; MR imaging, functional neuroimaging, and spectroscopy. (Dr. Hyde)
MR imaging and spectroscopy; computerized image processing by means of Fourier transforms. (Dr. Jesmanowicz)
Electron spin resonance studies of oxygen radicals and reactive nitrogen species in biological systems; major areas of interest include cardiovascular and neuro-degenerative pathologies (atherosclerosis, hypertension, ALS, Alzheimer’s, etc.), free radicals in apoptosis and signal transduction, and chemotherapeutic drug-induced toxicity. (Dr. Kalyanaraman)
Protein structure and functional dynamics studies using site directed spin labeling electron paramagnetic resonance spectroscopy. (Dr. Klug)
Functional magnetic resonance imaging studies of Alzheimer’s disease and drugs of abuse. (Dr. Li)
Proton magnetic resonance spectroscopy studies of brain tumors, Huntington’s disease. Dynamic phosphorus spectroscopy of muscle function. Imaging of lithium in bipolar disease. (Dr. Prost)
In vivo quantification of tissue perfusion using exogenous and endogenous contrast agents coupled with magnetic resonance imaging. (Dr. Schmainda)
Determination of functionally related brain regions for gastroenterological processes. (Dr. Shaker)
Spin label studies on membrane dynamics and organization (raft-domain formation), spin label oximetry and NO-metry. (Dr. Subczynski)
Investigation of pathophysiological mechanisms enhancing free radical formation from nitric oxide synthase in vascular cells and their relation to the tetrahydrobiopterin pathway. (Dr. Vasquez-Vivar)
Use of non-invasive imaging technologies to enhance the diagnosis and therapies for cancer and cardiovascular diseases. (Dr. Zhao)
Overall Course Requirements
A requirement of this program is to fulfill two credits in Bioethics by completing Course (10222) Ethics and Integrity in Science and Course (10444) Research Ethics Discussion Series. For course descriptions of 10222 and 10444 see listing within the Bioethics Program.
The Biophysics Graduate Program consists of two main tracks:
Molecular Biophysics includes studies on the physiology and pathology of biological free radicals and the use of stable radicals and metal ions to probe enzyme structure and function.
Magnetic Resonance includes functional neuroimaging of the brain, hardware development, image production, signal processing and analysis and magnetic resonance spectroscopy.
The Biophysics Program offers a number of courses in each of the two tracks. All graduate students in Biophysics are required to take the Biophysics Seminar and Biophysics Journal Club. Additional courses may be taken from the Basic Science and Clinical departments throughout the Medical College and also from Marquette University and the University of Wisconsin–Milwaukee.
I. Molecular Biophysics Track
This track is a component of the Interdisciplinary Program in Biomedical Sciences (IDP). After completing the first-year IDP Program, students will take the following courses:
03223 Electron Spin Resonance. 3 credits.
The aim of the course is to provide an introduction to the theory and practical applications of modern electron spin resonance (ESR) spectroscopy. Basic ESR theory, biological free radical spectroscopy, relaxation and motional phenomena, spin labeling and transition metal ESR are among the topics covered.
03226 Biophysical Techniques in Biochemistry. 3 credits
This course will introduce the basic theory and practical applications of an array of biophysical techniques commonly used in biochemical research. Optical and magnetic spectroscopies, X-ray crystallography and kinetics techniques are a sampling of the topics covered in this comprehensive course.
03251 Free Radicals in Biology. 3 credits.
Topics to be discussed include: the nature of free radicals; radical initiation, propagation, termination; free radical reactions of biological interest; and the role of free radicals in physiological and pathological processes.
Electives offered on an as-needed basis.
03220 Introduction to Magnetic Resonance. 3 credits.
The course provides basic knowledge for students who will continue to study ESR or NMR. The material covers magnetic resonance of the hydrogen and helium atoms, NMR spectra in liquids, basic ESR of radicals in solution, trapped radicals in solids, triplet states, spin relaxation, molecular rate processes, and double resonance. An understanding of matrix elements, eigenvalues, angular momentum, and tensor vector is recommended.
03242 Techniques in Molecular and Cell Biology. 2 credits.
This course is designed to expose graduate students to the technical and practical aspects of techniques currently used in molecular and cell biology
03254 Advanced X-Ray Crystallography. 3 credits.
The student will receive both didactic lectures on the physics of X-ray diffraction, diffraction symmetry, reciprocal space, crystals and their diffraction properties; and calculations related to the actual solution of a crystal structure. All students will make extensive use of a computer in the laboratory exercises leading to the total solution of a crystal structure for a biologically active molecule composed of 20-30 atoms. Heavy atom and probability-based structure solutions will be explored.
03260 Special Topics in Molecular Biophysics. 3 credits.
This is an advanced course dealing with special topics including free radicals in biology, spin relaxation, metal ions in biology, X-ray crystallography, and photobiology.
II. Magnetic Resonance Imaging Track
03230 Nuclear Magnetic Resonance. 3 credits.
This course is designed as an introduction to nuclear magnetic resonance (NMR) and nuclear magnetic resonance imaging (MRI). Emphasis will be given to theory and application of modern MRI techniques.
03238 Magnetic Resonance Imaging. 3 credits.
This is a course on the physics of modern MRI. It will take a classical approach to spin physics and will focus on pulse sequences, K-space analysis and hardware. An understanding of calculus is required, and Fourier analysis is recommended.
03239 Functional MRI Contrast Mechanisms and Applications. 3 credits. Prerequisite: 03238.
The use of magnetic resonance imaging (MRI) to evaluate tissue function will be described. The course will be dedicated to discussing functional MRI (fMRI) methods that use both endogenous contrast (labeled water, deoxygenated blood) and exogenous (injectable) MR contrast agents to image tissue function. The theory and physiology necessary for understanding the MR contrast mechanisms, together with the practical knowledge necessary for performing the MR experiments, will be discussed. Demonstrations of functional MRI experiments will be included.
03240 Fourier Transforms. 3 credits.
Material covers theory of Fourier transforms, digital transforms, nuclear magnetic resonance images, reconstruction, pulse spectroscopy methods, and electrical signal processing. An understanding of calculus and tensor vectors is recommended.
03298A Journal Club: EPR. 1 credit.
EPR Journal Club is a required course for Molecular Biophysics graduate students. It is offered each spring and fall semester, and introduces students to the various aspects of EPR via published studies in the scientific literature. Course Directorship is rotated each semester. The Course Director (CD) selects a topic for the semester, and each student selects one or more published papers pertaining to that topic, in conjunction with the CD. Selected papers are distributed to the class for prior reading. Each student presents their selected paper(s) to the class, along with any introduction to the area of study, and the class critically reviews the paper. Students will encounter aspects of EPR that they may not have previously encountered through either classes or their research, but which may be of value to their doctoral research or future research, teaching, or other careers.
03298B Journal Club: MRI. 1 credit.
Selected papers in theory, practice, and applications of electron and nuclear magnetic resonance will be read and discussed in separate sessions.
03301 Seminar. 1 credit.
Weekly invited seminar speakers present their research on Molecular Biophysics and Magnetic Resonance Imaging topics.
03295 Reading and Research. 1-9 credits.
03299 Master’s Thesis. 6 credits.
03399 Doctoral Dissertation. 9 credits.