The 6th Annual BME Symposium in Quantitative Biology and Physiology
Friday, February 12, 2010
Life Science and Engineering Building (24 Cummington Street) Rm. 103
Program
- 1:00 pm – Solomon Eisenberg (BME Chair)
Opening Remarks - 1:10 pm – David Hall
Modeling of protein complexes by docking - 1:30 pm – Christopher Garay
Constraint of genome-scale metabolic models of Mycobacterium tuberculosis with gene expression data - 1:50 pm – Jane Zhang
Rapid point-of-care concentration of infectious bacteria in a disposable microfluidic device using evaporation-induced meniscus dragging effect - 2:10 pm – Keith Wong
Cyclic AMP normalizes the function of engineered human microvessels in microfluidic collagen gels - 2:30 pm – Coffee Break
- 3:00 pm – Keynote – Dr. David Mooney, Harvard University
Materials to program cells in situ for regeneration and immunotherapy - 4:30 pm – Jesse Lock
Modeling, stability, and control of concentric tube robots - 4:50 pm – Walter Heine
A quantitative analysis of the retinal ganglion cell spatial receptive field properties in the brown norway rat - 5:10 pm – Solomon Eisenberg (BME Chair)
Closing Remarks
Abstracts
1:10 pm – David Hall
Modeling of protein complexes by docking
We focus on the problem of determining the structure of complexes formed by the association of two proteins by searchingfor the global minimum of a function approximating the free energy of the complex. Solving this problem requires a multistage approach. First we explore the conformational space by systematic global search based on the Fast Fourier Transform (FFT) correlation approach that evaluates the energies of billions of docked conformations on a grid. We show that the method can be efficiently used with pairwise interactions potentials that substantially improve the docking results. The 1000 best energy conformations are clustered, and the 30 largest clusters are retained for refinement. We also discuss the application of the combined method to recent targets in CAPRI (Critical Assessment of Protein Interactions), the first community-wide docking experiment, and the Protein-Protein Docking Benchmark. Additionally, we will briefly discuss the new ClusPro server and its performance in CAPRI as a fully automatedversion of our methods.
1:30 pm – Christopher Garay
Constraint of genome-scale metabolic models of Mycobacterium tuberculosis with gene expression data
The causative agent of tuberculosis (TB) is Mycobacterium tuberculosis (MTB), which currently infects approximately one-third of the world’s population. The spread of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) presents serious roadblocks to controlling the proliferation of this disease. In order to overcome limitations involved in experimental work in anti-TB drug development, we present the use of a genome-scale computational model of TB metabolism.More specifically, we employ a previously-validated method called E-flux that enables the use of gene expression array data to directly constrain the reactions in a flux balance analysis model of MTB.Using this method, we are able to make predictions about the physiological processes underlying latency and pathogenesis.
1:50 pm – Jane Zhang
Rapid point-of-care concentration of infectious bacteria in a disposable microfluidic device using evaporation-induced meniscus dragging effect
We report a low cost, disposable polymer microfluidic sample preparation device to perform rapid concentration of bacteria from liquid samples using enhanced evaporation induced meniscus dragging effect, targeted at downstream detection using surface enhanced Raman spectroscopy (SERS). The device is composed of a poly(dimethylsiloxane) (PDMS) liquid sample flow layer, a reusable metal air flow layer, and a porous PTFE (Teflon) membrane sandwiched in between the liquid and air layers.The concentration capacity of the device was successfully demonstrated with fluorescently tagged Escherichia coli (E.coli). The recovery concentration was above 90% for all initial concentrations lowerthan 6.3 x 105 CFU/ml. In the lowest initial concentration cases, 100μL initial volumes of bacteria solution at 100 CFU/mL were concentrated into 500 nL droplets with greater than 90% efficiency in 15 min.Subsequent tests with SERS on clinically relevant methicillin sensitive Staphylococcus aureus (MSSA) after concentration in this device proved more than 100-fold enhancement in SERS signal intensity compared to the signal obtained from the unconcentrated sample.
2:10 pm – Keith Wong
Cyclic AMP normalizes the function of engineered human microvessels in microfluidic collagen gels
Nearly all engineered tissues must eventually be vascularized to survive. To this end, we and others have recently developed methods to synthesize extracellular matrix-based scaffolds that contain open microfluidic networks. These scaffolds serve as templates for the formation of endothelial tubes that can be perfused; whether such microvascular structures are stable and/or functional is largely unknown. Here, we show that compounds that elevate intracellular concentrations of the second messenger cyclic AMP (cAMP) strongly normalize the phenotype of engineered human microvessels in microfluidic type I collagen gels. Cyclic AMP-elevating agents promoted vascular stability and barrier function, and reduced cellular turnover. Under conditions that induced thehighest levels of cAMP, the physiology of engineered microvessels in vitro quantitatively mirrored that of native vessels in vivo.Computational analysis indicated that cAMP stabilized vessels partly via its enhancement of barrier function.
This work was supported by the National Institute of Biomedical Imaging and Bioengineering (award EB005792).
3:00 pm – Keynote – Dr. David Mooney, Harvard University
Materials to program cells in situ for regeneration and immunotherapy
There are hundreds of clinical trials of cell therapy currently underway but simple cell infusions lead to large-scale cell death, little control over cell fate, and a typically poor clinical outcome. We propose a new approach, in which material systems are first usedeither as cell carriers or attractors of host cell populations, and in either case the material then programs the cells in vivo and ultimately disperses the cells to participate in regeneration orimmunotherapy.
4:30 pm – Jesse Lock
Modeling, stability, and control of concentric tube robots
Non-invasive intracardiac surgeries hold great promise for many patients with severe heart disease. A robotic system to accomplish this goal would need to be narrow, flexible, dexterous and provide superior tip position and force control than can be achieved with catheters. This type of flexible robot can be created by concentrically combining pre-curved elastic tubes. As the tubes are extended and rotated with respect to each other their individual curvatures interact to form a composite curvature along the length of the combined tubes. By manipulating the proximal ends of these tubes, the position and orientation of the distal end can be controlled. In the most general formulation, the equilibrium conformations of the tubes satisfy a two-point boundary value nonlinear differential equation. Furthermore, some conformations can be dynamically unstable. Those phenomena appearing in the model may include various types of tube deformation (bending, torsion, shear, elongation), friction and nonlinear hysteretic constitutive behavior. The challenge for robotics is to derive models that provide sufficient detail for robot design, but are also simple enough to enable real-ime control. This research describes the introduction of tube torsion into existing bending models to both improve model accuracy and to predict unstable conformations as well as an approximate model formulation that I have developed to facilitate real-time control.
4:50 pm – Walter Heine
A quantitative analysis of the retinal ganglion cell spatial receptive field properties in the brown norway rat
Rodents have become a popular animal model for studying assorted ocular disorders. Much work has been done characterizing the anatomical properties of rat retinal neurons with relativelylittle effort being spent on quantitative analyses of their physiological properties. In this study we examined the spatial receptive fields of different types of rat retinal ganglion cells (RGCs). Our results provide a foundation for the use of the rat as a model system for investigating retinal pathophysiology and the development of various therapeutic approaches. We demonstrate the presence of linear and nonlinear RGCs which appear analogous to X and Y cells found in other animals. The spatial frequency response of many of these cells was unimodal however some cells displayed bimodal tuning curves, indicating a more complex receptive field structure. The DOG model provided estimates of center and surround receptive field properties of cells with unimodal tuning curves. Rat RGC receptive field properties share many similarities with those ofcats and higher mammals, including center-surround organization, some orientation sensitivity, and linear and nonlinear spatial summation.
