Graduate Seminar Series
Every week at 11:30 AM • ENGR 406
See below for exact dates
Dr. Nicholas Dickenson — 11/15/2017
Identification and Characterization of Critical Shigella Type Three Secretion System Regulatory Proteins
Wednesday, November 15, 11:30 AM • ENGR 406
Many Gram-negative pathogens, including Shigella spp., use conserved type three secretion systems (T3SS) as key virulence factors. The Shigella T3SS relies on an associated needle-like type three secretion apparatus (T3SA) which penetrates the host cell membrane and provides a unidirectional conduit for injection of effectors into host cells. The rapid emergence of multi-drug resistant strains from this family of pathogens underscores the need to better understand not only the specific T3SS mechanisms supporting virulence, but to identify potential targets for non antibiotic based therapeutics. We are currently studying several potential targets, including surface exposed T3SS tip protiens that appear to play critical roles in environmental sensing and maturation of the apparatus as well as a recently identified T3SS ATPase that is required for proper protein secretion and apparatus secretion. Mechanistic and therapeutic implications for Shigella and related pathogens will be discussed.
Dr. Monica Serban — 9/06/2017 — "Engineering of Natural and Synthetic Biomaterials for Medical Applications"
Biomaterials, synthetic or natural, are the preferred building blocks for therapeutics and medical devices, because of their excellent biocompatibility. Two such building blocks – hyaluronan (HA), a glycosaminoglycan abundant in mammalian extracellular matrices, and silk fibroin (SF), an insect derived polymeric protein – have been extensively functionalized to present various biological clues; however, few of such approaches sought to synergistically build on the endogenous cellular interactions of these macromolecules. Specifically, native HA has been reported to have antagonistic effects in inflammatory processes depending on the macromolecule’s molecular weight. One of our projects is aimed at building on this fact and further engineer large molecular weight HA to have dual antioxidant and anti-inflammatory effects. These functionalized molecules will be explored as therapeutics for cytomegalovirus induced hearing loss (pathology with a reactive oxygen species-induced inflammation etiology). Similarly, we are exploring the effect of SF secondary structure on its interactions of SF with biological substrates prior to further functionalizing the molecule for in vitro diagnostics and other medical applications. In parallel, our laboratory is exploring other materials - such as starch-derived glucaric acid polymers or tetraethyl orthosilicate thixogels - as novel drug delivery systems.
Dr. Ryan Jackson — 9/13/2017 — "CRISPR RNA-guided adaptive immunity in Escherichia coli"
Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) adaptive immune systems, that protect bacteria and archaea from invasive viruses and plasmids, have recently been repurposed for a myriad of genetic engineering tools. In search of additional CRISPR-based genome editing tools, and to better understand crRNA-guided DNA interference in E. coli, we determined the 3.24 Å crystal structure of the 405 kDa multi-subunit Cascade (CRISPR associated complex for antiviral defense) complex. The Cascade structure reveals that a 61-nucleotide CRISPR derived RNA (crRNA) assembles with eleven proteins into a seahorse-shaped complex. Proteins at opposite ends of the complex bind conserved sequences at the 3’ and 5’ ends of the crRNA, while the guide sequence is displayed in five-nucleotide segments across a helical assembly of six interwoven subunits. Using additional structures of Cascade bound to nucleic acid targets, we performed molecular dynamics simulations that predicted functional roles in dsDNA binding for residues in the tail, backbone, and belly of Cascade, which we confirmed biochemically in vivo and in vitro. Additionally, we used architectural information to design longer Cascade complexes that bind DNA with higher specificity. Collectively, our results explain the mechanisms that drive target-induced conformational changes in Cascade upon DNA binding, reveal specific residues important for non-self target recognition, and directed the design of elongated complexes that may be used for gene regulation.
Dr. Eric W. Schmidt — 9/20/2017 — "Bioinspired Design Principles for Synthetic Biology of Organic Compounds"
One of the goals of synthetic biology broadly defined is to use genetic engineering methods to rationally produce desired chemicals or compound libraries. Hindering this goal is an imperfect understanding of the intrinsic promiscuity of biosynthetic pathways. We have sought naturally plastic biosynthetic pathways to natural products, aiming to understand the fundamental principles that enable promiscuity. By applying these principles, we have designed new materials aimed at drug discovery.
Dr. Jia Zhao — 9/27/2017 — "Computational Modeling of Multiphase Complex Fluids with Applications in Biological Engineering"
Complex fluids are ubiquitous in nature and in synthesized materials, such as biofilms, mucus, synthetic and biological polymeric solutions. Modeling and simulation of complex fluids has been listed as one of the 21st century mathematical challenges by DARPA, which is therefore of great mathematical and scientific significance.
In this talk, I will firstly explain our research motivations by introducing several complex fluids examples, and traditional modeling techniques. Integrating the phase field approach, we then derive hydrodynamic theories for modeling multiphase complex fluid flows. Secondly, I will discuss a general technique for developing second order, linear, unconditionally energy stable numerical schemes solving hydrodynamic models. The numerical strategy is rather general that it can be applied for a host of complex fluids models. All numerical schemes developed are implemented in C2FD, a GPU-based software package developed by our group for high-performance computing/simulations. Finally, I will present several applications in Biological Engineering, like cell motions on substate with nano/microtopography, and antimicrobial treatment of biofilms on dental plaque. 3D numerical simulations will be given as well. The modeling, numerical analysis and high-performance simulation tools are systematic and applicable to a large class of problems in science and engineering.
Dr. Frank Sachse — 10/04/2017 — "Advanced Microscopy Approaches to Study the Normal and Diseased Heart"
Confocal microscopy is a crucial imaging technology used in biomedical research and many other research fields. Confocal microscopy allows non-destructive imaging of three-dimensional structures and functions of cells and tissues at sub-micrometer scale. The temporal resolution of confocal microscopy is up to thousands of images per second, which allows studies of fast processes in cells and tissues. Recent technical developments triggered clinical translation of confocal microscopy for interventional and intraoperative imaging.
I will give an overview of our research at the Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, which extensively applies confocal microscopy. I will provide an introduction to confocal microscopy systems and relevant optical principles. Foci of the talk will be on the three-dimensional imaging of the infarcted heart and in-vivo imaging of cardiac tissue microstructure using fiber-optics confocal microscopy. I will describe tools for analysis of microscopic imaging data that we develop and apply in our research projects. I will discuss technical challenges related to application of confocal microscopy based approaches in research and clinical cardiology.
Dr. Alex Shcheglovitov — 11/08/2017 — "Modeling human brain development and disorders using iPSC-derived neurons and organoids"
Modeling human brain development and disorders using iPSC-derived neurons and organoids
Wednesday 11:30 AM • ENGR 406
Human cerebral cortex is a complex brain structure associated with many human-specific behaviors and disorders. My laboratory studies the development of this structure under normal and pathological conditions using human induced pluripotent stem cells. In my presentation, I will discuss our previous study of Phelan-McDermid syndrome (Shcheglovitov et al., 2013) and our recent progress towards the development of a new model for studying human cortical development using three-dimensional cortical organoids.