USU Summer Research
Training Program 2017
Cutting Edge Research
Seminar Series
Overview:The goal of this lecture series is to demonstrate and experience the language and organization that scientists use to convey and share ideas and data with each other and with the public. Each lecture in the series is given by current Postdoctoral Fellows from various departments. These Fellows are highly trained in their disciplines and perform complex experiments to test their hypotheses. Their lectures will be examples of real-world cutting-edge science. This series is designed to increase and deepen each student's understanding of her or his own summer research and will aid student preparation of a poster highlighting their research, culminating in a Capstone Poster Session at the end of the Program.
Date / Time / Room / Lecture Topic / InstructorTh, June 22 / 11 am / G252 / Resistance to ionizing radiation in microorganisms / Dr. RokTkavc
Th, June 29 / 11 am / A2053 / Using Super-Resolution Microscopy to See Ever-Smaller Biological Structures / Dr. Maria Traver
Th, July 6 / 11 am / A2053 / New approach into developing a gonorrhea vaccine / Dr. Adriana Le Van
Th, July 13 / 11 am / G252 / Host and Reservoir Immune Responses to Emerging Viruses / Ms. Chelsi Beauregard, EID
Th, July 20 / 11 am / A2053 / An O26:H11 Escherichia coli Fast-food Outbreak Strain that Makes Shiga toxin (Stx) type 1a and Stx2a is Highly Virulent in a Mouse Model of Infection. / Dr. Courtney Petro
Th, July 27 / 11 am / A2053 / The Regenerative Response from Neural Stem Cells and Progenitor Cells after Experimental Traumatic Brain Injury / Dr. Genevieve Sullivan
Th, Aug. 3 / 11 am / A2053 / Studying the effects of human pathogenic mutations in Mitochondrial RNase P complex using in-vivo Drosophila models / Dr. Maithili Saoji
Th, Aug. 10 / 11 am / TBD / Mode of Action and Functional Regulation of Human Multidrug Resistance P-glycoprotein (ABCB1) / Dr. Debjani Mandel
Th, Aug. 17 / 11 am / TBD / Small groups to share posters / multiple faculty
Friday, August 18 - USRTP 2017 Capstone Poster Session, 1-3pm, USU Cafeteria
June 22: Dr. RokTkavc, Dept. of Pathology, USUHS
Title:Resistance to ionizing radiation in microorganisms: What do we know so far and how can we use what we know?
Description:Ionizing radiation (IR) is present everywhere around us. Cosmic rays and the decay of radioactive isotopes are the primary sources of natural IR. However, IR can also be generated artificially using X-ray tubes, particle accelerators, and various radioisotope production methods. All organisms inhabiting this planet are resistant to IR to a certain extent. The most IR resistant organism reported so far is the bacterium Deinococcusradiodurans which can survive 12,000 Gy, 2400 times higher doses of gamma-radiation than humans can survive (5 Gy). Over the past few decades, many researchers have tried to unravel the mystery of Deinococcus’s extreme IR resistance. The in-depth genome, proteome, transcriptome, and genetic analyses of IR-resistant microorganisms have failed to provide us any reasonable explanation, until Dr. Daly and collaborators discovered that Deinococcus is able to protect its proteome (including DNA repair proteins) with simple organic and inorganic molecules. This discovery changed the fundamental paradigm of radiobiology and lead to several applications that will be presented in this lecture.
June 29th: Dr. Maria Traver, Dept. of Microbiology & Immunology
Title: Using Super-Resolution Microscopy to See Ever-Smaller Biological Structures
Description: It was over 400 years ago that researchers such as Zacharias Jansen, Anton van Leeuwenhoek, and Robert Hooke discovered that a vast array of life forms existed that were invisible to the naked eye. Using and improving on homemade, crude arrays of lenses, these men demonstrated that even a single drop of water was teeming with life, and that we ourselves are made of tiny cells like the rooms within a house. Building upon these long-ago discoveries, researchers today have vastly improved microscope technology to peer inside cells themselves, examining the structures (“organelles”) within. Nowadays, every high school biology classroom has microscopes capable of examining subcellular structures; but what if we want to see even further? What if we want to see how these organelles are themselves constructed? Can we see individual proteins? What about individual molecules? Today we will discuss the history of microscopy, learn about the newest, cutting edge microscope technology, and apply these techniques to the understanding of how the human immune system works.
July 6th: Dr. Adriana Le Van, Postdoctoral Fellow, Dept. of Microbiology and Immunology
Title:New approach to developing a gonorrhea vaccine
Description: Neisseria gonorrhoeae (Gc) is a gram negative diplococci and the causative agent of the disease gonorrhea. It is an obligate human pathogen and it infects over 800,000 people in the US alone each year. Gccolonizes the urogenital tract of both men and women causing urethritis and epididymitis in men and cervicitis in women. In about 10% of women infected, Gccan ascend to the upper reproductive tract leading to pelvic inflammatory disease, ectopic pregnancy and sterility. The emergence of Neisseria gonorrhoeae strains that are resistant to first line antibiotics has made the development of a gonorrhea vaccine an urgent matter. New
insights into the immune response against Gcinfections and the focus on conserved surface antigens have brought new light on gonorrhea vaccine research. Our laboratories are developing peptide-based vaccines against two outer membrane proteins: the GcPorB and MtrE proteins using a virus-like particle (VLP) vaccine delivery system. PorB plays a role in nutrient acquisition, epithelial cell invasion, antibiotic resistance and serum resistance. Gcstrains express one of two porBalleles, porB1a or porB1b. We have identified five synthetic PorB loop peptides that elicit antibodies that recognize a diverse collection of Gcstrains, bind to the Gcsurface, and are bactericidal against highly serum resistant strains. The MtrCDE active efflux pump protects Gcfrom innate host defenses. The importance of this pump during genital tract infection is supported by the demonstration that it is critical for experimental infection of female mice (Jerse 2003). In previous studies, we showed that a linear peptide to one of the two surface-exposed MtrE loops elicited antibodies (Abs) that bound the bacterial surface and were bactericidal. However, subcutaneous or intranasal immunization of mice with these PorB or MtrE peptides did not produce a mucosal Ab response, therefore, it requires an antigen delivery system that elicits high-titer vaginal Abs. We have characterized the serum antibody response to chemically conjugated PorB and MtrE loop peptide-VLPs as measured by ELISA and optimized an immunization regimen for inducing both serum and vaginal antibody responses.
July 13th: Chelsi Beauregard, a PhD candidate, Dept. of Microbiology and Immunology
Title:Host and Reservoir Immune Responses to Emerging Viruses
Description:In the last twenty years our world has seen dozens of new pathogens emerge and cause disease in humans and important agricultural animals. Of these emerging pathogens, a large percentage are viruses. We have seen devastating disease and high mortality rates from emerging viruses like Ebola, SARS, HIV, Avian influenza, Hendra, and Nipah, to name a few. All of these viruses have something in common. Each is harbored by wild animals but have “spilled over” into humans and other animals and caused disease. Animals that harbor a virus but do not get sick are called reservoirs, while animals that get sick from the same pathogen are called hosts. If history is any indication, there are many more pathogens that we have not yet seen cause disease but that may in the future. Without knowing what is to come it is hard to predict how we may treat new diseases. To circumvent this, our lab focuses on understanding the immune response to these emerging pathogens in reservoirs and comparing those responses to the immune response of a host. In our lab we study bats as reservoirs and use Australian bat lyssavirus (ABLV) as a model virus.ABLV and other Lyssaviruses like rabies virus are uniformly lethal in humans. In bats however, this disease can persist without pathogenesis. We use cell lines from humans and the bat Pteropusalectoand examine inflammatory pathways like autophagy (how a cell trashes viruses and damaged proteins) and NF-kB signaling (responsible for cell survival and control of production of pro-inflammatory proteins). If we can find places where the immune system of a reservoir and host differ, it will reveal potential factors to target and modify to improve infection outcome.
July 20th: Dr. Courtney Petro, Postdoctoral Fellow, Dept. of Microbiology and Immunology
Title: An O26:H11 Escherichia coli Fast-food Outbreak Strain that Makes Shiga toxin (Stx) type 1a and Stx2a is Highly Virulent in a Mouse Model of Infection.
Description:Stx-producing E. coli (STEC) cause food-borne outbreaks of diarrhea. Stxs are some of the most potent bacterial toxins known and play an essential role in virulence of STEC. Stxs are encoded on lysogenic bacteriophages. Stress, such as treatment with some antibiotics, induces the bacteriophage and increases Stx production. The two major types of Stx produced by STEC are Stx1a and Stx2a. Although Stx1a is more toxic than Stx2a on tissue culture cells, Stx2a is more potent than Stx1a in mice. In late 2015, an STEC fast-food outbreak was traced to an stx1a+ stx2a+ O26:H11 STEC strain. We have characterized this strain along with another less virulent STEC strain. We have determined that levels of Stx1a and Stx2a may predict severity of virulence in a mouse model of infection.
July 27th: Dr. Genevieve Sullivan, Postdoctoral Fellow, Dept. of Anatomy, Physiology and Genetics
Title:The Regenerative Response from Neural Stem Cells and Progenitor Cells after Experimental Traumatic Brain Injury.
Description:The subventricular zone (SVZ) is a region of the brain where neural stem cells (NSCs) and progenitor cells reside. NSCs and progenitor cells have the potential to repair the brain following traumatic brain injury (TBI); however, the response of NSCs to repair damaged tissue is often insufficient. Therefore, patients with moderate and severe TBI often suffer with permanent disability.
Analysis of brains from TBI patients often shows damage chronically persists in white matter regions, which contain many neuronal axons that are myelinated by oligodendrocytes. The corpus callosum is a white matter region that is located adjacent to the SVZ germinal niche in both humans and mice. Therefore, we modified a mouse model of traumatic axonal injury (TAI) to produce damage in the axons of neurons, demyelination, and inflammation, primarily in the corpus callosum, in order to study the regenerative response from NSCs and progenitor cells located in the SVZ and in the corpus callosum. Previous work outside our lab has shown NSCs in the SVZ respond to sonic hedgehog (Shh) signaling, which has important regenerative roles. Thus, we utilized transgenic mice to label NSCs responsive to Shh after TAI. We investigated the response of the labeled NSCs out to 6 weeks post-TAI. Surprisingly, labeled NSCs were not detected in the corpus callosum following TAI. Additionally, labeled NSCs in the SVZ were decreased 2 weeks following TAI, but returned to baseline levels by 6 weeks post-TAI. Axon damage, myelin abnormalities and inflammation persisted out to 6 weeks post-injury. These findings indicate the NSC in the SVZ are negatively impacted by TAI; and with progenitors, NSCs are unable to repair the damaged CNS by 6 weeks after TAI. Therefore, the TAI model is useful for investigating therapeutic strategies to promote repair following TBI. Furthermore, modifying the NSC response through Shh signaling may be an effective strategy for enhancing repair.
August 3rd: Dr. Maithili Saoji, Postdoctoral Fellow, Dept. of Biochemistry and Molecular Biology
Title: Studying the effects of human pathogenic mutations in Mitochondrial RNase P complex using in-vivo Drosophila models
Description:Mitochondria are considered to be the powerhouse of the eukaryotic cell.It is widely accepted that, millions of years ago, when the eukaryotic cells were still evolving, specialized bacterium got trapped within the cell, co-existing in a symbiotic relationship and evolving into the present day mitochondria. Mitochondria are the major sites of ATP production, and play a key role in cell signaling and apoptosis. Mitochondrial dysfunction is associated with several diseases like cardiovascular and neurological disorders. Like bacteria, mitochondria have a copy of their own circular DNA. The mitochondrial DNA (mt DNA) is highly similar in all eukaryotic species, andencodes for 13 proteins involved in respiration along with the ribosomal and transfer RNAs (mttRNA), required for the synthesis of these proteins. Interestingly, even though only ~9% of the mt DNA encodes for the mttRNAs (explain what is tRNAs), point mutations in this region cause disproportionately large number of mitochondrial diseases, with symptoms like cardiomyopathy and hypertension. During the process of transcription, in which the DNA is decoded to RNA, mt DNA is transcribed as a continuous RNA transcript. The long RNA is then cleaved precisely into different mt mRNA, mttRNA and the mtrRNA, post-transcriptionally by several enzymes to form the final products. In Humans, Mitochondrial Ribonuclease P (MRPP), is one of the processing factors that cut the tRNA at its 5’end and release it from neighboring protein coding transcript. MRPP is a three complex made up of MRPP1, MRPP2 and protein only RNase P (PRORP). The PRORP is the catalytically active subunit while the exact role of MRPP1 and 2 is still unclear. The MRPP proteins are critical in humans, as evidence suggests that mutations in this complex cause heart diseases. Our lab studies the Drosophila (fruit fly) homologs of the MRPP complex proteins: Roswell (MRPP1), Scully (MRPP2) and Mulder (PRORP), to understand the effect of human pathogenic mutations in these proteins, in relation to cardiovascular diseases. We demonstrated that each of these proteins function in the mitochondria and are required for survival of the fly. Loss of each of these proteins is associated with mitochondrial deficits and lead to defective tRNA processing. Currently, we are generating fly lines with human pathogenic mutations in MRPP to study their effect on tRNA processing and in turn on mitochondrial function and tissue homeostasis. Using our in-vivo fly model we strive to advance our understanding on tRNA processing linked human mitochondrial diseases.
August 10th: Dr. Debjani Mandel, Dept. Biochemistry and Molecular Biology
Title: Mode of Action and Functional Regulation of Human Multidrug Resistance P-glycoprotein (ABCB1)
Description:The human multidrug transporter P-glycoprotein (Pgp or ABCB1) sets up pharmacological barriers to many clinically important drugs, a therapeutic remedy for which has yet to be formulated. Functionally, Pgp is an ATP-dependent efflux pump for an inordinately wide range of structurally unrelated hydrophobic drugs including anti-cancer and anti-HIV agents and contributes to drug resistance in about 50 percent of human cancers by preventing accumulation of powerful anticancer drugs in cancer cells.
For the rational design of mechanism-based inhibitors (or modulators), it is necessary to map the potential sites for modulator interaction and understand their modes of communication with the other functional domains of Pgp. Combining directed mutagenesis with molecular modeling, we identify two modulator-selective sites at thelipid-protein interface of Pgp, through which essential steps like ATP hydrolysis and substrate binding are functionally modulated.