Cell biophysics. Cell mechanics of adhesion, migration and dynamics. Immunophysics and immunoengineering. Hyaluronan glycobiology. Hyaluronan synthase. Physics of tissues.
The Curtis lab is primarily focused on the physics of cell-cell and cell-extracellular matrix interactions, in particular within the context of glycobiology and immunobiology. Our newest projects focus on questions of collective and single cell migration in vitro and in vivo; immunophage therapy "an immunoengineering approach - that uses combined defense of immune cells plus viruses (phage) to overcome bacterial infections"; and the study of the molecular biophysics and biomaterials applications of the incredible enzyme, hyaluronan synthase.
A few common scientific themes emerge frequently in our projects: biophysics at interfaces, the use of quantitative modeling, collective interactions of cells and/or molecules, cell mechanics, cell motility and adhesion, and in many cases, the role of bulky sugars in facilitating cell integration and rearrangements in tissues.
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.
The biomechanics of locomotion of organisms and robots on and within complex materials. Physics of granular media.
My research integrates my work in complex fluids and granular media and the biomechanics of locomotion of organisms and robots to address problems in nonequilibrium systems that involve interaction of matter with complex media. For example, how do organisms like lizards, crabs, and cockroaches cope with locomotion on complex terrestrial substrates (e.g. sand, bark, leaves, and grass). I seek to discover how biological locomotion on challenging terrain results from the nonlinear, many degree of freedom interaction of the musculoskeletal and nervous systems of organisms with materials with complex physical behavior. The study of novel biological and physical interactions with complex media can lead to the discovery of principles that govern the physics of the media. My approach is to integrate laboratory and field studies of organism biomechanics with systematic laboratory studies of physics of the substrates, as well as to create mathematical and physical (robot) models of both organism and substrate. Discovery of the principles of locomotion on such materials will enhance robot agility on such substrates.
Physics of soft materials with a focus on the connection between microscopic order and macroscopic properties.
Soft materials are materials whose properties are determined by internal structures with dimensions between atomic sizes and macroscopic scales. They are characterized by energies that are typically comparable to kT. As a result, they have low elastic moduli, often ~1-10 Pascals. Typical soft materials include liquid crystals, polymers, colloidal suspensions and emulsion drops. These materials, unlike conventional simple liquids, are locally heterogeneous and can have broken symmetries that affect their physical properties. Hence, although they often exhibit liquid-like behavior, soft materials also often exhibit properties of solids. Our laboratory studies the physics of soft materials with a focus on the connection between microscopic order and macroscopic properties. The underlying theme is to pursue basic understanding and address fundamental questions. However, we also address applied problems and pursue industrial collaborations since many of the materials we study can be viewed as model systems for those that are often used in applications. Current projects include (i) studying the phase and non-equilibrium behavior and properties of dense microgel suspensions, (ii) understanding the consequences of confinement and curvature over the equilibrium states of ordered materials, which in many cases require the existence of topological defects in their ground states, and (iii) electrohydrodynamics of toroidal droplets and jets.
Complex systems and excitable media, experimental physiology, high performance computing and GPU
High performance computing:
· Development and implementation of novel algorithms to solve partial differential equations in two- and three-dimensional regular and irregular domains.
· Computer modeling of complex systems using supercomputers, as well as graphics cards (GPUs).
· Simulations and large data visualization of complex systems in or near-real time locally or over the web.
Experiments in complex systems:
· Cardiac dynamics. Study the voltage and calcium dynamics of cardiac tissue using heart sections or whole hearts from fish and mice to large mamals horses. Using voltage- and calcium-sensitive dyes and ultrafast cameras, we record the dynamics of voltage and calcium waves and study their instabilities associated with arrhythmias.
· Dynamics of spiral and scroll waves.
· Mechanisms of bifurcation and period-doublings in time and in space.
· Methods for chaos control and synchronization.
· Chemical, physical, and other biophysical oscillators with complex dynamics and instabilities. Examples: spiral and scroll waves in the Belousov–Zhabotinsky reaction, saline oscillator.
Mathematical modeling of complex systems:
· Development and analysis of mathematical models that describe generic or detailed dynamics of excitable and oscillatory media (heart, neurons, chemical reactions, calcium signaling, physical and biological oscillators, etc.).
· Study of bifurcations and chaotic (organized and disorganized) dynamics of excitable and oscillatory systems.
· Develop and apply control methods for suppressing or synchronizing complex dynamics.
· Study of stability and instabilities of spiral waves and three-dimensional scroll waves in idealized and realistic domains of excitable media.
In most projects there is crossover between theory, simulations and experiments, where experiments (simulations) are used to guide theory and simulations (experiments).
A central challenge for many organisms is the generation of stable, versatile locomotion through irregular, complex environments. Animals have evolved to negotiate almost every environment on this planet. To do this, animals' nervous systems acquire, process and act upon information. Yet their brains must operate through the mechanics of the body’s sensors and actuators to both perceive and act upon the environment. Our research investigates how physics and physiology enable locomoting animals to achieve the remarkable stability and maneuverability we see in biological systems. Conceptually, this demands combining neuroscience, muscle physiology, and biomechanics with an eye towards revealing mechanism and principle -- an integrative science of biological movement. This emerging field, termed neuromechanics, does for biology what mechatronics, the integration of electrical and mechanical system design, has done for engineering. Namely, it provides a mechanistic context for the electrical (neuro-) and physical (mechanical) determinants of movement in organisms. We explore how animals fly and run stably even in the face of repeated perturbations, how the multifuncationality of muscles arises from their physiological properties, and how the tiny brains of insects organize and execute movement.