Biological Physics

Experimental Biological Physics

Nanomedicine

Research activities in Kattesh Katti’s group involve the development of engineered nanoconstructs with capabilities for site specific targeting of receptor proteins over expressed in breast, pancreatic and prostate cancers. The overall goal has been to target tumor specific peptide functionalized gold nanoparticles on cancer cells/receptors and lesions to be able to detect breast, pancreatic and prostate cancers in early stages through sophisticated molecular imaging.  The high Z value of gold is being capitalized for the X ray CT imaging of various tumors. The efficacy of the engineered gold nanoparticles toward endocytosis within cancer cells has allowed accurate detection of circulating tumor cells (CTCs) from breast, pancreatic and prostate cancers via Photoacoustic techniques with detection limits reaching 1-10 cancer cells. Radioactive gold nanoparticles (Au-198/199) are inherently therapeutic; through comparative oncology efforts, the group has succeeded in developing targeted therapeutic gold nanoparticles which have shown unprecedented therapeutic efficacy reaching >85% in reduction of tumor volumes in both small animals and in dogs which mimic human prostate tumors.

The group has pioneered  in the application of ‘Green Nanotechnology’ for the development various phytochemical-based tumor specific diagnostic and therapeutic nanoparticles. Latest results published in the Proceedings of the National Academy of Sciences (2012) describe prostate tumor specific epigallocatechin-gallate(EGCg: abundant green tea)-functionalized radioactive gold nanoparticles, when delivered intratumorally (IT), will circumvent transport barriers, resulting in targeted delivery of therapeutic payloads. This innovative “green nanotechnological” approach serves as a basis for designing target specific antineoplastic agents. This novel intratumorally injectable 198AuNP-EGCg nanotherapeutic agent may provide significant advances in oncology because it offers the best pathway for the destruction of tumor and cancer stem cells—thus ablating localized and also metastatic lesions in various types of tumors.

The group is also developing nanoparticles-based new therapeutic approaches for the treatment of age related macular degeneracy (AMD) and Pseudo Xanthoma Elasticum (PXE).

Single Molecule Biophysics

Gavin King addresses fundamental problems in biophysics via precision single-molecule measurement apparatus. Specifically, he is developing and implementing a unique ultrastable atomic force microscope (AFM) to elucidate the structure, structural energetics, and conformational fluctuations of membrane proteins. A central question is: How does the dynamic structure of these proteins influence their function? An ultrastable AFM complements traditional characterization techniques by providing an atomically precise means to address this question in physiologically relevant conditions.

Theoretical Biological Physics

Statistical Thermodynamics and Kinetics of RNA and Protein Folding

Shi-Jie Chen’s group studies the statistical thermodynamics and kinetics and computer modeling of biomolecules and polymers, particularly RNA & protein folding. Biological molecules are large organic molecules composed of hundreds or thousands of atoms bound together by covalent bonds into a chain-like structure. One of the best known challenges in biology is to understand how biomolecules fold properly into compact structures to perform biological functions and how they mis-fold to cause disease. A fundamental problem his group is pursuing is the study of the physical principles that govern folding-unfolding of bio-molecules. Based on the physical principles, the group is developing statistical mechanical theories and computational models that can make accurate predictions for the sequence-structure and structure-activity relationships for biomolecules. This involves statistical physics, computer simulations and, of course, mathematics.

Theoretical and Computational Biological Physics

The main motivation and goal of Ioan Kosztin’s research in biological physics is to understand how living matter is organized and functions at different (e.g., atomic or microscopic, sub-cellular or mesoscopic) levels. In his research, he employs and develops computational methods widely used in molecular modeling (e.g., large scale, parallel molecular dynamics simulations, molecular visualization, stochastic modeling and analysis), as well as, analytical methods used in theoretical physics. The type of problems currently researched in his group are related to: mechanical force generation and signaling mechanisms in G-proteins, force transduction by motor proteins, effect of static and dynamic disorder (thermal fluctuations) on energy transfer in light harvesting proteins, mass and charge transport in transmembrane channel proteins, reconstruction of potential of mean force from non-equilibrium molecular dynamics simulations, and aggregation phenomena in biological systems.

Computational Drug Design

Protein – ligand interactions and protein-protein interactions are widespread critical processes in cellular functions and macromolecular assemblies. The ability to predict these interactions will have a far reaching impact on understanding the mechanisms of these important biological processes. A prominent application is rational design of drug molecules that can bind to the catalytic site of the target protein (e.g., in bacteria and cancer cells). Xiaoqin Zou’s research group works on physics-based modeling of protein-ligand and protein-protein interactions. The group’s ongoing research program includes the following projects: (1) Development of physical models to evaluate protein-ligand and protein-protein binding free energies. This requires accurate modeling of complex molecular interactions such as electrostatic interactions, van der Waals interactions, and entropic effects. (2) Structure-based inhibitor/drug design. For a given known protein (drug target), the group screens for chemical compounds that can form low-free energy complexes with the target protein. These compounds could become therapeutic drug candidates for clinical trials if they pass toxicity and metabolism tests. (3) Modeling structure-function relationship for membrane proteins. Membrane proteins play crucial structural and functional roles in cellular and physiological processes. Xiaoqin Zou also investigates the mechanisms of membrane protein functions from structural and thermodynamic analysis, and facilitate experimental design to enhance or degrade the membrane protein functions through mutagenesis or intervention of agents.