In this lecture, Dr. Greg Underhill explains the relations of stem cell fate in correspondence to biosensors. The lecture starts out with a brief introduction of stem cells and a liver and pancreas differentiation. In the endoderm, some stem cells become pancreas cells, while only a hundred microns away others become liver. The question being asked is what controls that differentiation. We then look at how a cell microarray can be used to find out the determining factor of what stem cells becomes pancreas or liver cells as there is a clear distinction in the place where the differences in these transformations take place. Then all the different Extracellular Matrix Microarray (ECM) proteins combinations with each other are looked at and they are printed to find out which are the proteins that the cell interact with best. It allows the endoderm adhesion to be viewed because stem cells differentiate with little changes and this allows us to see which cells will stick with which proteins. If the cell is not on the right ECM and you induce liver, for instance, those cells can just die and set up differentiating. ECM combinations are crucial and can lead to synergistic or antagonistic affect that you would not be able to anticipate. If the cells are on the right ECM, they can better respond to the soluble factors that are around the cell. Current and future studies for these ECM Microarrays are then looked at. Then, we move on to looking at how stem cells respond and behave in a third-dimensional environment. A Large Particle Cytometer was then discussed and how it can be used to analyze the results of these third-dimensional cell behaviors. The high throughput examination in Vivo is then looked at. The idea of multiplexing, which is performing multiple experiments at the same time in parallel, is discussed. The lecture concludes looking at current and future studies of multiplexing for high throughput for ECM output.
My research group is focused on the application of sub-wavelength optical phenomena and fabrication methods to the development of novel devices and instrumentation for the life sciences. The group is highly interdisciplinary, with expertise in the areas of microfabrication, nanotechnology, computer simulation, instrumentation, molecular biology, and cell biology. In particular, we are working on biosensors based upon photonic crystal concepts that can either be built from low-cost flexible plastic materials, or integrated with semiconductor-based active devices, such as light sources and photodetectors, for high performance integrated detection systems.
Using a combination of micrometer-scale and nanometer-scale fabrication tools, we are devising novel methods and materials for producing electro-optic devices with nanometer-scale features that can be scaled for low-cost manufacturing. Many of our techniques are geared for compatibility with flexible plastic materials, leading to applications such as low cost disposable sensors, wearable sensors, flexible electronics, and flexible displays. Because our structures manipulate light at a scale that is smaller than an optical wavelength, we rely on computer simulation tools such as Rigorous Coupled Wave Analysis (RCWA) and Finite Difference Time Doman (FDTD) to model, design, and understand optical phenomena within photonic crystals and related devices.
In addition to fabricating devices, our group is also focused on the design, prototyping, and testing of biosensor instrumentation for high sensitivity, portability, and resolution. Advanced instruments enable high resolution imaging of biochemical and cellular interactions with the ability to monitor images of biochemical interactions as a function of time. Using the sensors and instrumentation, we are exploring new applications for optical biosensor technology including protein microarrays, biosensor/mass spectrometry systems, and microfluidics-based assays using nanoliter quantities of reagents. The methods and systems developed in the laboratory are applied in the fields of life science research, drug discovery, diagnostic testing, and environmental monitoring. -From Professor Cunningham's Faculty Profile
Research in the Underhill laboratory is aimed at understanding how combinatorial signals in local microenvironments guide stem cell differentiation in development and regeneration. We also have a strong interest in how microenvironmental regulation mechanisms contribute to the pathogenesis of cancer and degenerative diseases. These efforts span the disciplinary boundaries between microfabrication, biomaterials, cell and developmental biology, and genomics, and are directed towards the development of novel cell-based therapeutic approaches in tissue engineering and regenerative medicine. A particular focus is on the design and implementation of high-throughput screening platforms and microtechnology systems for the tightly controlled presentation and analysis of microenvironmental cues. Specific research areas include: (1) developmental patterning processes in organ development, and the role of signaling gradients in tissue specification and stem cell differentiation, (2) bi-directional cell-cell interactions between distinct tissues (e.g. liver and blood), and their importance in cell differentiation and tissue formation, (3) cell-cell interactions in the adult during regeneration processes and in tissue engineering transplantation contexts, and (4) microenvironmental regulation of tumor development and pathogenesis.
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