Kopriva Graduate Student Fellowship Recipients
Joanna-Lynn Borgogna studies the microbes that inhabit the human vagina (vaginal microbiota) and provide the first line of protection against potential pathogens of the female reproductive tract. Bacterial vaginosis (BV) is the most common vaginal disorder among reproductive-aged women, having been estimated to affect 21.2 million (29.2%) of all U.S. women. BV is associated with an increased risk of adverse health outcomes, including increased acquisition of various bacterial and viral sexually transmitted infections, as well pregnancy complications. Borgogna is developing statistical techniques to model the vaginal microbiome, metabolome and associated metadata with the ultimate goal being to improve our understanding of the biochemistry and micro-ecology of the vaginal environment and its relation to infection and disease.
Timothy Borgogna studies how influenza A infections leave a host in an immunocompromised state and increase susceptibility to secondary bacterial pneumonia by Staphylococcus aureus. S. aureus, commonly referred to as a “superbug” for its propensity to quickly acquire antibiotic resistance, has an innate ability to sense and respond to surrounding environments. Infection with influenza A may alter the lung environment in a manner that induces S. aureus pathogenesis through tightly controlled regulatory systems within its genome. SaeR/S is a two-component regulatory system demonstrated to be essential in S. aureus pathogenesis following influenza infection. Borgogna is part of a research group exploring how S. aureus senses and responds to various host environments and immune responses.
Jonathan Martinson studies how bacteria in the microbiome persist and adapt in the human gut. Escherichiacoli is a ubiquitous member of the human microbiome, yet little is known about the intrinsic factors that allow this species to colonize nearly all people on Earth. To determine these factors, Martinson collected hundreds of fecal samples from eight healthy adults over a two-year period. With these samples, he isolated and preserved over 30,000 E. coli clones and found long-lived ‘resident’ populations that persisted within a volunteer for months to years. He has found that more diverse microbiomes are more likely to carry resident E. coli. With the E. coli clone collection, Martinson has also performed full genome sequencing and metabolic tests to determine what allows resident populations to persist for long periods in the human gut.
Barbour is developing new statistical methods for constructing clinical scales that can detect smaller temporal changes in disease progression with more sensitivity than any single available scale. When establishing clinical trial outcomes, it is difficult to quantify the level of disease severity and progression in neurological disorders, such as multiple sclerosis (MS), due to their biological complexity. An improved ability to detect changes in disease severity will allow for more economical screening of therapeutic drugs in clinical trials, such as those underway for MS. Read more…
Rachel Rawle studies the metabolic processes in gut bacteria that mediate arsenic-related disease development. On both a domestic and global scale, arsenic contamination in soil and water has become a serious issue resulting from both industrial and natural geologic sources. It is estimated that over 200 million people worldwide consume arsenic-tainted water at levels above the health limit set by the Environmental Protection Agency. The ultimate goal of this research project is to provide information that can be used to develop prophylactic treatments or probiotics that use microbes to lessen the toxic effects of arsenic to humans. Read more…
Paul van Erp
Paul van Erp studies adaptive immune systems in bacteria and archaea. Known as CRISPR-systems (clustered regularly interspaced short palindromic repeats), these immune systems protect bacteria from invading genetic elements such as viruses. Specifically, van Erp’s research focuses on the immune system in Escherichiacoli. In this system, a RNA-protein complex called Cascade recognizes viral DNA and recruits an enzyme called Cas3 which destroys the viral DNA. He is trying to understand in molecular detail how these “protein machines” find and destroy foreign DNA. Read more…
Arianna Celis studies heme, the complex of iron and the organic molecule protoporphyrin IX that is one of the most ancient and ubiquitous biological molecules. She is working on a recently discovered pathway for heme biosynthesis that is unique to several bacteria, including many important pathogens. This pathway ends in a step catalyzed by an unusual enzyme known as HemQ. Celis is studying the mechanism by which the HemQ in Staphylococcus aureus, a leading cause of bacterial infections of human skin and soft tissues, performs its function at the chemical and cellular levels. Researchers hope this work will result in a molecular-level understanding of HemQ’s role in Staphyloccocus aureus, which may be applicable to a full range of pathogens identified as emerging or relevant to biodefense such as Methicillin-resistant Staphylococcus aureus, Mycobacterium tuberculosis, Bacillus anthracis and others. Read more…
Amanda Fuchs investigates the interactions between bacterial biofilms and human macrophages, a type of immune cell. Bacterial biofilms consist of densely packed communities of microbial cells that grow on living or inert surfaces. Biofilms are more resistant to antibiotic treatment and are known to evade the immune system. Bacteria residing within chronic wounds, such as diabetic foot ulcers, often form biofilms and have been shown to cause a significant delay in the healing time and closure of wounds due to excessive inflammation. A macrophage is a type of white blood cell found in most bodily tissues, where they survey the area for foreign substances, microbes and cellular debris. It is speculated that macrophages are primarily responsible for the resolution of inflammation in wounds. Fuchs is studying the metabolites and metabolic pathways involved in the interactions between Pseudomonas aeruginosa biofilms and human macrophages to gain insights into the cellular mechanisms contributing to persistent inflammation in chronic wounds. Read more…
Amanda Byer investigates one of the largest enzyme super families that exists in all domains of life: the radical S-adenosyl-L-methionine (SAM) enzyme superfamily. When human radical SAM enzymes fail, it can lead to diseases such as viral infection, diabetes mellitus, impaired cardiac and respiratory function, congenital heart disease and cofactor deficiency. Through a SAM and iron-sulfur cluster moiety, radical SAM enzymes generate a radical, or unpaired electrons, which can be destructive in biological systems if uncontrolled. Byer's research uses various spectroscopic techniques to examine radical SAM enzyme active-sites and identify how radical chemistry is constrained by the protein environment in these organometallic biochemical systems. Read more…
Caffrey researches the early immune response against Aspergillus fumigatus, a common mold that can be found in soil or compost piles. The mold causes severe lung infections in people with weakened immune systems, perhaps compromised by leukemia, chemotherapy or organ transplants. The death rate from Aspergillus fumigatus ranges from 30 to 90 percent, depending on the population. To help lower that percentage and understand what goes wrong in weakened immune systems, Caffrey studies healthy immune systems to see how they respond to Aspergillus fumigatus. She has discovered that a molecule called IL-la is critical for recruiting white blood cells to an infection site. Read more…
Willems studies lipid abnormalities in Alzheimer’s disease (AD), nonalcoholic fatty liver disease and Type 2 diabetes, all which may be related to disregulation of metabolism. Lipid disregulation has been implicated in many brain disorders such as AD, Parkinson’s, depression and anxiety. Willems has developed an effective set of protocols to extract and analyze the lipid fraction of metabolites found in many tissues. By applying these techniques to human brain tissue, he can search for early biomarkers of the development of Alzheimer’s disease. Further, he hopes to be able to detect these biomarkers in blood plasma at relevant levels and early detection in blood would be a key to better treatment and prolonged life. Read more…
Heberling’s research focuses on mathematical modeling and numerical analysis. She is currently modeling transcription, which is the first step of gene expression when a particular segment of DNA is copied into RNA by the enzyme RNA polymerase. During transcription, RNA polymerases are known to frequently pause for short lengths of time. In the high density setting, where there are many polymerases transcribing the gene in a line, the transcriptional pauses can cause a “traffic jam” of polymerases on the DNA strand. A mathematical analysis of this phenomenon will lead to a greater understanding of the cause and effect of these pauses on gene expression and regulation. Read more…
Manrique studies the role of viruses in shaping the structure and function of the bacterial communities associated with the human gut. Changes in the gut microbiome composition and structure negatively impact human health, and correlate with important diseases such as diabetes and cancer. Her research focuses on defining the role of viruses associated with the human gut microbiome in affecting human health and disease. She has isolated viruses from human samples, directly sequenced the isolated viral genomes, and applied advance bioinformatics analysis to understand the viral community composition and temporal dynamics in the human gut. Read more…
Timothy Hamerly has developed a novel method for isolating small molecules from complex solutions using serum albumin, a protein found in the blood stream that transports a wide variety of small molecules throughout the body. His method greatly reduces the number of molecules seen by a mass spectrometer, resulting in decreased time spent analyzing data and increased rates of biomarker discovery. Hamerley’s assay has also been used to differentiate stressed animals that have undergone hemorrhagic shock (massive blood loss) from healthy animals in a rapid manner. Read more…
Nick Dotson studies how different areas of the brain interact during working memory. This is accomplished by recording neural activity from non-human primates that are performing a working memory task. Deficits in working memory are a hallmark of many cognitive disorders, such as schizophrenia, and this type of work is crucial for the development of better treatments and diagnostic tools. The results of his research, which shows that that the patterns of synchronization between the prefrontal and posterior parietal cortex retain information in working memory, were recently reported in the journal Science. Read more…
Sydney Akapame’s research is focused on the optimal design of nonlinear models, which are models with exponents, logarithms or other complicated functions of the independent variable and parameters, for biostatistical applications. His work has been applied to the design of optimal experiments for testing compartmental models of drug absorption rates in pharmacokinetic studies, as well as models used to study chemical reactions that are catalyzed by enzymes and logistic models used in many pharmaceutical applications. Read more…
Joshua Heinemann studies metabolism, and is focused on developing technology that will allow researchers to measure changes in metabolism in “real-time” using microfluidics and mass spectrometry. Using this technology living cells are processed and directly measured for changes associated with disease and stress. Development of this technology is important for preemptive treatment or intervention of disease. Microfluidic technology also has the advantages of low cost components and biocompatibility allowing direct integration into a living system. Read more…
Shefah Qazi works with P22 virus-like particles as next-generation diagnostic tools for medical resonance imaging (MRI) of cardiovascular diseases. Her research focuses on modifying the interior and exterior surfaces of P22 virus-like particles for both encapsulation of small molecule imaging agents and targeted delivery of these agents to diseased tissues. The P22 platform demonstrates a significant increase in contrast over clinically used MRI contrast agents. This research may lead to earlier detection and treatment of cardiovascular related diseases. Read more…
Alison O’Neil works with protein shells, which are found in diverse organisms and may provide blueprints for functional nano- and biomaterials design. Specifically, her research is focused on the development of a new class of bio-inspired materials that use the directed confinement of enzymes (or other proteins) within viral protein cage assemblies. While the encapsulated enzymes retain their native catalytic activity, the protein cage can be separately optimized as a container. These nano-reactors have varied applications in biomedicine and energy production. Read more…
Amy Servid is part of a team of researchers using protein cage nanoparticles to provide protective immune responses against respiratory viruses. Servid’s research focuses on characterizing and modifying these nanoparticles with the goal of understanding how the structure of the nanoparticles relates to their function in vivo. She uses chemical and genetic modifications to design nanoparticles that display antigens or targeting molecules. This research provides a foundation for the design of nanoparticles that offer enhanced protection against influenza and other respiratory viruses. Read more…
Jonas Mulder-Rosi is studying how the functions of nerve cells depend upon their shapes and intrinsic biochemical properties. This research will assess how the normal healthy functioning of a nerve cell is determined by various structural and biophysical properties, which is a significant consideration from basic and clinical perspectives. Mr. Mulder-Rosi will use his fellowship to purchase computer hardware needed for his research and to attend conferences to present his results.
Crystal Richards’ research is focused on water and biofilms as an exposure pathway to pathogenic bacteria, including Helicobacter pylori, on the Crow Indian Reservation. This research will provide useful data to the Crow Reservation about drinking water quality, and increase understanding of H. pylori physiology in drinking water. She used her fellowship to attend an international conference, and to purchase supplies and books to support her research.
Travis Harris’ research is focused on understanding the intimate details of biological nitrogen fixation, which could lead to improved agricultural fertilizers that are more sustainable and less destructive to the environment. Mr. Harris used his fellowship to collaborate with researchers in Utah, to attend the International Conference on Biological Inorganic Chemistry in Japan, and to purchase computer hardware allowing him to perform work while away from campus.
Sunshine Silver used her fellowship to study an enzyme found in spore-forming bacteria. The enzyme enhances the bacteria’s resistance to ultraviolet light, making it very difficult to kill these organisms which can threaten human health with a number of diseases.
Ramon Tusell used his fellowship to develop techniques for modeling protein functions in the human body. Each human gene codes for a specific protein molecule (chain of amino acids) that performs a specific task, but how the proteins achieve these tasks is not well-understood at the atomic level.