I am interested in understanding (i) how transcription factors find their targets on DNA and activate transcription despite the presence of nucleosomes and (ii) how structural details of trans-activators and cis-elements quantitatively fine-tune gene regulation at the cellular level.
The Harold Kim Lab is an experimental biophysics group studying the biophysics of the genome in the School of Physics at Georgia Institute of Technology. A meter-long DNA is tightly packaged into chromosomes inside a micron-wide nucleus of a cell. Therefore, the genetic information is difficult to locate and process. Despite this formidable challenge, cells constantly convert the genetic code into appropriate amounts of proteins in a timely manner based on external signals. This interesting phenomenon is at the core of our research.
Dr. Jang's research interest is to characterize and design nanoscale systems based on the molecular architecture-property relationship using computations and theories, which are especially relevant to designing new biomaterials for drug delivery and tissue engineering. Currently, he is focusing on 1) NanoBio-mechanics for DNA, lipid bilayer, and hydrogel systems; 2) Molecular interaction of Alzheimer proteins with various small molecules. Dr. Jang is also interested in various topics such as nanoelectronics, nanostructured energy technologies for fuel cell, battery and photovoltaic devices.
Our laboratory has diverse research interests including: evolutionary synthetic biology, molecular biology, comparative genomics, computational biology, bioinformatics, biomedicine, molecular evolution and origins of life, and evolution and engineering of protein thermostability.
Engineering Nuclear Hormone Receptors. Nuclear hormone receptors control the expression of genes in response to small molecule hormones. In performing this activity, the receptors must specifically recognize small molecules, DNA, and other proteins. The amino acids that recognize each of these substrates are varied using genetic engineering techniques until a receptor with novel recognition is created. The original and new receptors are studied using a variety of biophysical techniques to elucidate the principles behind the new activity. This exercise provides both new knowledge for future protein engineering and real materials for research and medical applications.
We engineer new receptors to turn on gene expression in response to specifically chosen small molecules. The small molecule may be chosen for its properties in the specific application. For applications in gene therapy and use as a tailored gene switch, the small molecule may be chosen due to its long or short pharmacokinetic half-life, because it crosses the blood-brain barrier, or other tissue specificity. For applications in synthetic biology gene circuits, the small molecule may be chosen for its interactions with other circuits in a network. Another application is in assembling the biosynthetic components (enzymes) to synthesize the small molecule via genetic selection.
Dr. Kim’s research focuses on developing biomimetic microsystems that reconstitute organ-level functions on chip and integrative control systems that allow large-scale production of therapeutic and diagnostic bio/nanomaterials. His lab develops experimental control systems and micro/millifluidic platforms, and employs computer-aided engineering to understand: (1) how cells coordinate responses to signaling cues in multicellular environments; (2) how bio/nanomaterials assemble and break in dynamically controlled fluid flows; and (3) how biological systems interact with nanomaterials with varied physicochemical properties.
Organs-on-chips that mimic the characteristics of human organs are enabling scientists to predict more accurately how effective therapeutic drug candidates would be in clinical studies without serious adverse effects and to address how multiple cells coordinate organizational decisions in response to complicated signaling cascades. Dr. Kim’s lab builds valid artificial organ-on-a-chip systems by manipulating 3D extracellular environments in time and space, utilizing the expertise in microfabrication, miniaturization, robotics, and control systems engineering, and understanding the human body’s fundamental physiological responses to mechanochemical cues. This research will help examine the behavior and interaction of multifunctional nanomaterials with biologically relevant microenvironments for rapid clinical translation of nanomedicine, thereby bringing drugs to market more quickly and perhaps even eliminate the need for animal testing.
Advanced treatment of diseases such as cancer and atherosclerosis needs controlled delivery of multifunctional nanocarriers that contain multiple drugs that can target tumors with anti-angiogenic and cytostatic agents and a diversity of imaging agents that monitor the transport in the body. Optimized integration of manufacturing nanomaterials will contribute to advanced health technology not only because of rapid clinical translation of drugs but also due to reduction of any release of harmful byproducts. Dr. Kim’s lab designs and fabricates diverse microfluidic modules for diverse syntheses of multifunctional nanomaterials and integrates the modules to establish large-scale implementation of manufacturing processes scaled to economically and industrially relevant production level. The integrative system will facilitate good manufacturing practice (GMP) production and clinical translation in pharmaceutical and biomedical industry and enable reproducible and controlled synthesis of nanoparticles at scales suitable for rapid clinical development and commercialization.
Dr. Gleason's current research interest is in soft tissue biomechanics and growth and remodeling, with particular emphasis on native vascular tissues and tissue engineered constructs. Two key aims of his research are to develop mathematical theories for soft tissue growth and remodeling that allow for the incorporation of observations made at multiple length scales, and to develop novel experimental models to test the underlying assumptions of theoretical simulations that allow for parallel observations at different length scales.
It is unquestioned that cells can sense and respond to changes in loading. Increased load on focal adhesion sites in vascular smooth muscle, for example, can alter cell-signaling pathways, ultimately leading to altered gene expression. Altered gene expression can manifest itself in many different ways, including an altered production of vasoactive molecules, extracellular matrix and matrix-degrading proteins, cell cycle regulating signals, and cytoskeletal proteins, among many others. The net effect of these, and other, mechanotransduction pathways include increases in cell and matrix turnover, local growth (or atrophy), structural and functional remodeling of existing cells, and remodeling of matrix, cell-matrix and matrix-matrix interactions, all aimed, presumably, toward evolving the local mechanical environment from an undesirable' condition to a desirable' condition. Despite the explosion of information on tissue growth and remodeling, from molecular, intracellular, cellular, cell-matrix, organ, and whole organism levels, attempts at integrating these data into a predictive model is still in its infancy; there is a pressing need for such an integrative, multiscale model. Such predictive models will be essential to further our understanding of many physiological and pathophysiological processes and critical to aid in the development and optimization of clinical interventions and tissue engineering strategies.
Dr. Ku has an active interest in peripheral vascular pathology and unsteady, threedimensional fluid dynamics. One project investigates the relative role of hemodynamics and thrombosis in vascular graft occlusion. Additional studies involve the development of a tissue-engineered vascular graft. Noninvasive magnetic resonance imaging is used to determine the hemodynamics and detect pathology in vivo. Computational solutions explore fluid mechanic variations from geometry. Another project studies the collapsible tube behavior of highly stenotic arteries.
Dr. Ku has an active interest in cardiovascular pathophysiology, unsteady threedimensional fluid mechanics, medical implants, and commercialization of university research. Basic research focuses on sudden cardiac death from platelets subjected to high shear and plaque rupture due to arterial stenosis collapse. His research extends to Translational Technology using applied biomedical engineering to impact patient care and therapy. Projects span from device design to development of bench tests to predict clinical performance. Dr. Ku teaches entrepreneurship and product development to bring technological solutions to the bedside.
Dr. Hesketh's research interests are in Sensors and Micro/Nano-electro-mechanical Systems (MEMS/NEMS). Many sensors are built by micro/nanofabrication techniques and this provides a host of advantages including lower power consumption, small size and light weight. The issue of manipulation of the sample in addition to introduce it to the chemical sensor array is often achieved with microfluidics technology. Combining photolithographic processes to define three-dimensional structures can accomplish the necessary fluid handling, mixing, and separation through chromatography. For example, demonstration of miniature gas chromatography and liquid chromatography with micromachined separation columns demonstrates how miniaturization of chemical analytical methods reduces the separation time so that it is short enough, to consider the measurement equivalent to "read-time" sensing.
A second focus area is biosensing. Professor Hesketh has worked on a number of biomedical sensors projects, including microdialysis for subcutaneous sampling, glucose sensors, and DNA sensors. Magnetic beads are being investigated as a means to transport and concentrate a target at a biosensor interface in a microfluidic format, in collaboration with scientists at the CDC.
His research interests also include nanosensors, nanowire assembly by dielectrophoresis; impedance based sensors, miniature magnetic actuators; use of stereolithography for sensor packaging. He has published over sixty papers and edited fifteen books on microsensor systems.