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Graduate Seminar Series

Every week at 11:30 AM • ENGR 406
See below for exact dates

Dr. Noelle G. Beckman — 12/06/2017

Nicholas DickensonAssistant, Utah State University 
Department of Biology & Ecology Center

 

Extinction Risk of Plant Species Under Global Change

Wednesday, December 6, 11:30 AM • ENGR 406

Abstract:

For plants, which are sessile for most life history stages, seed dispersal is an essential process. Global change affects the ecology and evolution of dispersal, limiting the ability of species to move or adapt to global change events. Aspects of dispersal ability may trade-off with other aspects of a life history strategy, such as reproduction. However, dispersal has not been incorporated explicitly into investigations of plant life history strategies. Quantifying the influence of dispersal on individual fitness and plant populations is challenging. Empirically, dispersal is difficult to observe, measure, and manipulate at the relevant scales needed to assess the full influence of dispersal. Analysis of spatial models with realistic assumptions about processes at multiple scales is a mathematical challenge. Incorporating dispersal into plant life history strategies and examining dispersal under global change will not only give us a better basic understanding of patterns of biodiversity and species distributions but also allow us to better predict species’ risk to climate change. Integrating empirical and quantitative approaches, my research contributes to an understanding of the mechanisms limiting plant populations and the influence of global change on these processes with consequences for plant communities and ecosystem functions.

 


Dr. Monica Serban — 9/06/2017 — "Engineering of Natural and Synthetic Biomaterials for Medical Applications"

Monica Serban

Assistant Professor, University of Montana
Department of Biomedical and Pharmaceutical Sciences

Abstract:

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"

Ryan Jackson

Assistant Professor, Utah State University
Department of Chemistry and Biochemistry

Abstract:

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"

Eric W. Schmidt

Professor, University of Utah
Department of Medicinal Chemistry

Abstract:

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"

Jia Zhao

Assistant Professor, Utah State University
Department of Mathematics

Abstract:

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"

Frank Sachse

Associate Professor, University of Utah
Department of Bioengineering

Abstract:

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"

Alex Shcheglovitov

Assistant Professor, University of Utah
Department of Neurobiology and Anatomy

Abstract:

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.

Dr. Nicholas Dickenson — 11/15/2017 — "Identification and Characterization of Critical Shigella Type Three Secretion System Regulatory Proteins"

Nicholas DickensonAssistant Professor, Utah State University 
Department of Chemistry and Biochemistry

 

Abstract:

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. C. Allan Guymon — 11/29/2017 — "Controlled Micro- and Nanostructured Biomaterials through Photopolymerization"

Nicholas DickensonAssistant Professor, Utah State University 
Department of Chemistry and Biochemistry

 

Abstract:

Photopolymerization has taken an increasing prominent role as a tool in providing unique properties for a wide array of advanced materials. The inherent spatial and temporal control allow great ability to tailor processing conditions and change ultimate properties. This talk will focus on two projects, including work from two Utah State alumni, in which photopolymerization enables directed structure both on the micron and nanometer size scale for unique functionality.

Photopolymerization has also enabled research to improve nerve regrowth and guidance to improve neural prostheses such as cochlear implants. We have used the spatial and temporal control inherent to photopolymerization methodology to fabricate micropatterned methacrylate polymers that direct nerve cell growth based on substrate topographical cues. Micropatterned substrates are formed in a rapid, single-step reaction by selectively blocking light with photomasks. The resultant pattern is a continuous series of parallel ridges and grooves at regular intervals and of various amplitudes that can be used for cellular contact guidance studies. Micro-feature depth is controlled and reproducibly generated from the nanometer to micron level by shuttering the light source at different time steps during the reaction. Regenerative growth of inner ear nerve cells orients to the direction of the micro-pattern and is strongly dependent on feature size and slope. Substrate stiffness is modified by varying the cross-link density of the final material by either increasing the amount of cross-linker in the prepolymer formulation or by increasing the size of the spacer unit between cross-links. Spiral ganglion neurites were observed to align more strongly as substrate rigidity increased. The ultimate goal of the research is to develop materials that predictably orient regenerative nerve cell growth and improve neural prosthetic stimulatory specificity and, thus, improve patient outcomes. Recent results also demonstrate that photo-grafted zwitterionic hydrogels substantially reduce protein and cellular adsorption, providing means to reduce fibrosis for cochlear implants.

The second topic will focus on generating nanostructure in organic polymers through photocuring in self-assembling lyotropic liquid crystals (LLC) as polymerization templates to direct polymer morphology.  The water- and oil-soluble domains inherent in the liquid crystal phase serve as a platform to segregate monomers into ordered geometries based on polarity.  The rapid polymerization kinetics of photopolymerization are then utilized to trap and thereby template the LLC structure.  Many useful property relationships are observed in the resulting nanostructured polymer systems such as concurrent increases in mechanical strength and swelling as well as increased solute release rates that are not observed in traditional polymer systems. This unique combination is particularly useful for tissue engineering platforms when enhanced transport and mechanical stability are needed including for materials in retinal regeneration. Additionally, the structure has a profound impact on stimuli-responsive properties of poly(N-isopropylacrylamide) with a two-fold increase in equilibrium water content and over two orders of magnitude decrease in deswelling time without compromising the strength of the material. These templated materials show a favorable increase in polymer properties and polymerization kinetics for systems photopolymerized in LLC phases useful in a wide-variety of applications ranging from drug delivery and tissue scaffolds to water purification.