Networks & Interactions
Biological systems consist of vast numbers of components connected by physical interactions between components and interactions with the environment. At Notre Dame, researchers study both individual components and their interactions in order to understand in a predictive way the fundamental principles that govern biological processes. Examples include: What interactions are important to ensure proper protein folding and enzyme function? What interactions cause some proteins to be prone to misfolding, leading to diseases such as cystic fibrosis, Alzheimer’s, and juvenile cataracts? How does the microtubule cytoskeleton, a dynamic network of protein fibers that directs chromosome segregation during mitosis, assemble and disassemble as needed? How do proteins recognize foreign and cancerous cells, and how does this recognition lead to cellular communication such as T cell function in the immune system? How do interactions between host cells and metastasizing cancer cells determine tumor growth? How does the lipid composition of specific membranes lead to recruitment of specific proteins, facilitating viral infection? How does development work on a molecular level? Analyzing these interactions at all levels, from individual molecules to larger networks, is improving our understanding of how biological systems are organized and controlled, including our ability to predict the effects of genetic mutations.
Notre Dame biophysicists develop and test computational models to predict the behavior of biological systems. These include models to study how the behavior and dynamics of lipid bilayers affects permeability for molecules entering and exiting a cell or organelle. Other groups develop models of disordered solids, complex networks, or population genetics and evolution using many-body theory and statistical mechanics. Enzyme-catalyzed reactions govern many biophysical processes, and Notre Dame researchers develop and test atomic-level, physics-based models of these reactions - both the enzymes and their substrates - to provide structural, dynamic, and energetic information that can define reaction mechanisms and identify promising drug targets. High-resolution models of spectroscopic measurements, including time-dependent excitation of fluorescent probe molecules, have enabled Notre Dame researchers to extend established experimental techniques to develop a deeper understanding of solvation dynamics and the microscopic motions of biomolecules. Computational modeling serves as an important tool to characterize and predict the behavior of many complex biophysical systems, and in many groups, predictions from computational studies are developed alongside experimental testing, creating a synergistic feedback loop to accelerate discovery.
Imaging & Structure
Creating a clear picture of a biophysical system offers many advantages for understanding its properties and functions. Notre Dame has extensive state-of-the-art instrumentation and facilities for biophysical characterization of macromolecules, including nuclear magnetic resonance spectroscopy and imaging, mass spectrometry and proteomics, calorimetry, surface plasmon resonance, fluorescence spectroscopy and microscopy, X-ray crystallography and single molecule imaging. Notre Dame researchers have developed novel mass spectrometric methods for charazterizing 3D cell culture systems, and other groups are developing molecular probes to allow researchers to see the effects of molecules in vivo for drug screening and binding studies. Researchers are developing atomic force microscopy and Raman spectroscopy instrumentation to selectively detect receptor binding of small molecules within a cellular membrane and characterize receptor target sites. Light transmission spectroscopy is used to investigate the size distribution of particles within cells to determine the governing principles of internal organization or to distinguish between normal and cancerous cells. Recent technical advances have increased our ability to resolve the size and shape of biomolecules in complex environments, allowing Notre Dame researchers to use structural properties to predict biomolucule function in healthy tissue and disease systems.
Affiliated Researchers: Brian Baker, Paul Bohn, Jessica Brown, Francis Castellino, Patricia Champion, Holly Goodson, Paul Huber, Amanda Hummon, Masaru Kuno, Sylwia Ptsasinska, Matthew Ravosa, Steven Ruggiero, Zachary Schultz, Bradley Smith, and Carol Tanner
Dynamics & Reactions
Biophysical systems are constantly undergoing change. Researchers at Notre Dame study these changes, resulting from either internal processes or external stimuli, to attack problems such as antibiotic resistance, stroke, or treatment of cancer. Researchers study the fibrinolytic pathway of hemostasis, specifically the plasminogen ligand binding mutants, to characterize the details of ligand/protein binding. Using transient optical spectroscopy, time-resolved resonance Raman, electron paramagnetic resonance, conductivity, and ambient pressure XPS, researchers can measure changes in aqueous solutions of biomolecules due to electron beam pulsing. Other groups study the role of dynamics in allosteric signaling, flexibility-activity relationship, and the evolution of protein function. Researchers have introduced low-energy, atmospheric pressure plasma jet (APPJ) radiation to complement existing radiation treatment for cancer in order to access an alternative pathway to cancer cell death. They also use dissociative electron attachment (DEA) to more clearly elucidate the efforts of ionizing radiation on amino acids, peptides, and protein structures. Building the experiements that will lead to a better understanding of how complex, dynamic, biophysical systems operate will lead to new discoveries on how to control these systems.