Biological and Medical Physics has been a significant research concentration within the Physics Department for more than 25 years. Highlights of the program include:
- Research on multiple levels from molecular (DNA, proteins) to tissue (heart muscle, brain)
- National and international collaborations
- Undergraduate Biomedical Physics program
- Biological physics seminar series sponsored by the Center for Interdisciplinary Research Center (CIRCS)
- Clinical applications of biomedical physics are taught via junior and senior level seminar courses in medical imaging, medical applications of lasers and optical techniques, and radiation therapy, given by expert practitioners from local hospitals and biotechnology companies
Professor Wanunu’s group studies biomolecular systems at the nanoscale (macromolecular and sub-molecular levels). One research direction is the development of force techniques by which biomolecular properties can be studied at the single-molecule level. The group fabricates very small (sub-5 nm) nanopores in synthetic membranes using a fine electron beam, and uses them to investigate the properties of clinically important biomolecules. A second research direction involves developing tools for monitoring enzymatic activity in realtime at the single-molecule level. Third, the group investigates the self-assembly of synthetic biomolecules on crystalline matrices, for bioelectronic and biomaterial applications. A wide variety of techniques is used in the lab, including micro- and nano-fabrication, organic and inorganic thin film deposition, interfacial chemistry and bioconjugate chemistry, scanning probe microscopy, vibrational spectroscopy, electronic/optical measurements, and more.
Force spectroscopy measurements in the laboratory of Professor Mark Williams use optical tweezers to manipulate single molecules and measure the forces required to stretch them. Measurements of these forces are used to determine the stability of the DNA double helix and the extent to which various DNA binding proteins alter the structure and stability of DNA. This approach provides unique insights into the function of these proteins in the cell.
Nuclear resonance vibrational spectroscopy (NRVS) reveals low frequency Fe vibrations that participate in biological reactions, on the basis of synchrotron measurements near the 14.4 keV Mössbauer resonance. This work is done by the group of Professor Tim Sage in collaboration with Wolfgang Sturhahn and Ercan Alp at the Advanced Photon Source and Professor Steve Durbin at Purdue University. Polarized infrared measurements in the laboratory of Professor Tim Sage yield precise molecular orientations and connect structural models derived from X-ray diffraction with conformational dynamics under physiological conditions.
Vibrational coherence spectroscopy measurements in the laboratory of Professor Paul Champion use ultrafast lasers to probe coherent low frequency oscillations of proteins. These measurements reveal the thermally driven motions that lead to reactions and the extraction of useful energy by proteins from random thermal excitations. The lab also studies the so-called “big bang” of biophysics; namely, the kinetics of diatomic ligand binding reactions to heme proteins. These measurements include a broad range of timescales from femtoseconds to milliseconds that are uniquely accessed using the laboratory’s advanced laser technology.
In the biological arena, Professor Alain Karma’s group’s efforts have focused on understanding basic mechanisms of “cardiac arrhythmias”, a term commonly used to describe irregular heart rhythms. Of particular interest is ventricular fibrillation, a turbulent rhythm that stops the heart from pumping and is the leading cause of sudden death among industrialized nations. Their recent studies have focused on elucidating cellular mechanism of calcium waves and triggered activity that make the heart susceptible to the onset of life-threatening arrhythmias and fibrillation.
Analysis of neural circuits in the cerebral cortex is the primary research focus of Prof. Armen Stepanyants’ group. This group is utilizing computational and theoretical methods of statistical physics in the attempt to uncover the basic principles governing the circuit organization and function. To date, many fundamental questions about the brain remain unanswered: How do neurons find appropriate synaptic targets in the course of development and form functional circuits? How do these circuits change during learning and memory formation? What is the connectivity diagram of the brain? Due to the unparalleled complexity of the brain, answering these questions requires new theories and computational methods and will undoubtedly lead to new discoveries.
Professor Albert-László Barabási heads the Center for Complex Network Research. His group’s research is aimed at elucidating the organizing principles that govern the complex emergence and behavior of a wide range of technological, biological, and social networks. His research on biological networks is aimed at understanding the complex interactions of elementary units in between the cell’s numerous constituents including proteins, DNA, RNA, and small molecules. This research exploits protein-chip and microarray gene expression data to study various metabolic, signaling and transcription-regulatory networks that emerge from these interactions and that are key for understanding the cell’s functional organization and human diseases.
Professor Vespignani is working on the development and refinement of computational techniques for the in-silico simulation of the spatial spreading of infectious diseases in structured populations. He is also engaged in the design, implementation, deployment, and maintenance of computational infrastructures for epidemics research. In particular Professor Vespignani has led the development of the Global Epidemic and Mobility (GLEaM) model that is a discrete stochastic epidemic computational model based on a meta-population approach in which the world is defined in geographical census areas connected in a network of interactions by human travel fluxes corresponding to transportation infrastructures and mobility patterns.
The Nanotechnology revolution has enabled novel approaches to addressing the major problems of disease diagnosis and therapy, leading to the emergence of Nanomedicine as a new paradigm for diagnosis and therapy. We have developed several nanoplatforms that offer potential for significant improvements in multi-modal imaging, targeted delivery of therapeutics, and monitoring of outcomes. Magnetic liposomal nanoplatforms for theranostics combine multiple functionalities including imaging, magnetic guidance to the disease site, delivery of the drug payload through sustained as well as triggered drug release. We have already demonstrated in vivo multimodal imaging using MRI, SPECT and FMT using these nanoplatforms.
Optical imaging is being applied for the optical biopsy of cancer, offering promise to detect precancerous lesions, to guide targeted therapies and to monitor cellular mechanisms of treatment escape. We are developing advanced spectroscopic imaging microendoscope technology in tandem with new molecular-targeted probes to enable multiplexed visualization of heterogeneous disease in mouse models of cancer, and ultimately in humans. This translational research program also incorporates photomedicine that bypasses classical mechanisms of resistance to DNA-damaging therapies, where antibody conjugates serve dual functions enabling high fidelity visualization and selective treatment of microscopic disease missed by surgery and chemotherapy. The ultimate goal of the program is to reduce cancer recurrence and mortality by establishing new approaches for personalized medicine that address tumor heterogeneity, drug-resistance and molecular mechanisms of treatment escape.
Prof. Bi’s group uses methods from theoretical and computation physics to study the mechanics of tissues and collective cell migration with broad applications to development, cancer metastasis and disease progression. In collaboration with experimental groups, a major focus is to understand the relationship between cell shapes and tissue-level mechanical response in respiratory diseases. Another focus is to understand the connection between cell level phenotypic heterogeneities in primary cancer tumors and metastatic behavior. The group also works together with developmental biologists on developing computational models to study the emergence of geometrical order during fruit fly morphogenesis.
In contrast to the molecular approach of Biophysics, Medical Physics focuses on the behavior of anatomical entities as a whole. Consequently it involves studies of healthy and diseased subjects, in both academic laboratory and hospital clinical settings. The research of Professors Aaron and Shiffman is an example, in which non-invasive electrical impedance measurements are used to assess the condition and activity of skeletal muscle. This has clear relevance to neuromuscular disease, and to general systemic disease via the mechanism of “chronic illness induced myopathy.” These aspects of the program are conducted in collaboration with physicians at local hospitals, while study of the physics underlying the measurements is the primary focus at the university.
Faculty with research interests in Biological and Medical Physics include Professors Ronald Aaron (Emeritus), Albert-László Barabási,Dapeng “Max” Bi, Paul Champion, Nathan Israeloff, Alain Karma, J. Timothy Sage, Carl Shiffman (Emeritus), Bryan Spring, Srinivas Sridhar, Armen Stepanyants, Alessandro Vespignani, Meni Wanunu, Paul Whitford, and Mark Williams.