Source: MONTANA STATE UNIVERSITY submitted to
EXPLORATORY RESEARCH ON INFECTIOUS DISEASES OF ANIMALS AND THEIR MANAGEMENT IN MONTANA
Sponsoring Institution
State Agricultural Experiment Station
Project Status
NEW
Funding Source
STATE
Reporting Frequency
Annual
Accession No.
1009679
Grant No.
(N/A)
Project No.
MONB00027
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Jul 1, 2016
Project End Date
Jun 30, 2021
Grant Year
(N/A)
Project Director
Voyich, JO, M.
Recipient Organization
MONTANA STATE UNIVERSITY
(N/A)
BOZEMAN,MT 59717
Performing Department
Microbiology & Immunology
Non Technical Summary
Infectious disease causes considerable loss for livestock producers by reducing production of animal units and by reduced sales because of food safety concerns. The Microbiology and Immunology (MBI) Department is the only research unit in Montana focused on animal health, particularly on the study of infectious diseases of cattle, bison and sheep. New faculty members joining MBI are required to initiate new research projects. In addition, other faculty not on Montana Agricultural Experiment Station (MAES) funding may be hired to develop new short-term projects. These projects are in support of the respective missions of MAES and MBI. This departmental project is to be used by these scientists to generate data to enhance their existing MAES project(s), take advantage of unique opportunities and to enhance their competitiveness for grant funding from federal agencies, such as the USDA. Support is also provided to maintain and operate departmental research facilities.Newly awarded MAES and/or initiated projects that have also been peer-reviewed include:1. Molecular pathogenesis of West Nile Virus (New MAES Project). West Nile virus (WNV) is an emergent neuroinvasive pathogen that causes severe illness in a wide range of vertebrates, including horses. In recently published work, we reported a restriction that limits the number of alphaherpes virions infecting neurons (Taylor et al., 2012). I propose a series of experiments that aim to identify if neuroinvasive spread of WNV is restricted in the number of virions transmitted between cells and characterize the cellular antiviral signaling activated neuronal infection of WNV. By characterizing neuroinvasive spread of WNV, we will begin to understand how neuroinvasive viruses are controlled during zoonotic infections and understand the impacts on viral population biology and pathogenesis. IBC Protocol Numbers: 032-2014 (WNV), 08-2015 (recombinant Baculovirus) and IACUC Protocol: 2013-282. Genome editing though use of CRISPR technology (New MAES Project). Cas9 is a new RNA-guide technology that permits rapid and precise manipulation of plant and animal genomes. This new gene knockout system is revolutionizing molecular biology and the value of this technology is currently estimated in the billions. However, this technique has been primarily restricted to generating gene knockouts (i.e. search and delete functions). Knockouts are critical for determining the biological function of a specific gene, but the genetic basis of many plant and animal diseases are already known and the next major advance will be to design methods that facilitate precise repair of defective genes (i.e. search and replace functions). Here we propose lentiviral delivery of Cas9 to generate a genome-wide knockout library in human cells that will identify novel pathways that enhance Homology Directed Repair (HDR) of double-stranded DNA breaks. We anticipate that many of the human genes involved in HDR will have conserved functions in other animals and plants. Results from this screen will provide fundamental new insight into DNA repair mechanisms, and provide a foundation for designing the next generation of tools for "correcting" genetic disorders and engineering Ag related products for resistance to environmental stress, and improving food security for the rapidly expanding population. IBC Protocol 024-2014.3. Mucosal immunology in pigs (NIH pilot grant peer-review). This study seeks to obtain pilot data to evaluate the current zoonotic threat and the mechanisms of gastric pathogenesis for human Helicobacter suis (H. suis) infection. H. suis is a stomach-dwelling bacterium naturally found in pigs that has been associated with gastric lesions including gastric cancer in humans. The overall hypothesis is that H. suis is a relevant zoonotic pathogen that disrupts human gastric epithelial cell function by triggering inflammatory signaling. In summary, our study will elucidate inflammatory pathways induced by H. suis and will determine whether there is a need for further research into zoonotic H. suis infection. IBC protocol 042-2014.4. New vaccine development for Coxiella and Brucella (new project). Using novel virus-like particles, unique vaccine constructs are being developed for effective T cell immune responses against Coxiella and Brucella.5. Disease ecology of pneumonia in bighorn and domestic sheep (new project).6. Plasmid curing project and studies of immunemodulators to reduce dependence on antibiotic use (new projects).
Animal Health Component
100%
Research Effort Categories
Basic
90%
Applied
10%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3113310109020%
3113410109010%
3113010100010%
3113999116010%
3153310109020%
3153410109010%
3153999116020%
Knowledge Area
311 - Animal Diseases; 315 - Animal Welfare/Well-Being and Protection;

Subject Of Investigation
3999 - Animal research, general; 3310 - Beef cattle, live animal; 3410 - Dairy cattle, live animal; 3010 - Honey bees;

Field Of Science
1090 - Immunology; 1160 - Pathology; 1000 - Biochemistry and biophysics;
Goals / Objectives
The short- and long-term objectives of research in Microbiology & Immunology (MBI) are the development of new drugs, vaccines, and diagnostic tools for fighting infectious diseases of livestock, humans, and wildlife. This includes scholarly discovery and dissemination of science and technology related to diseases affecting livestock and wildlife, as well as zoonotic diseases that can be transmitted to humans. MBI projects have specific objectives that lead to scientific accomplishments and programmatic growth through increased grant and contract activity. It is expected that all MAES-funded projects eventually become funded by extramural sources. This increased extramural funding leads to sustainable increases in graduate student and research associate numbers. Results will be disseminated through published scholarly activity and various outreach activities.
Project Methods
MBI scientists utilize state-of-the-art molecular approaches to address basic and applied problems in infectious disease research. These research programs require laboratories, large and small animal facilities, clinics, and modern research equipment, such as flow cytometers, DNA sequencers, and genomics analysis facilities. The study of agents, such as B. abortus require BSL-3 facilities approved for Select Agent work. Specific methods and procedures utilized are dependent upon program type and necessary protocols. New or existing faculty members must develop an understanding of Montana and regional issues and a more in-depth understanding of existing research programs, prior to developing their own MAES project proposals. This departmental project is to be used by these scientists to generate data to enhance their existing MAES project(s), take advantage of unique opportunities and to enhance their competitiveness for grant funding from federal agencies, such as the USDA. Support is also provided to maintain and operate departmental research facilities. All research will have appropriate IBC Protocol Numbers and IACUC Protocol approvals.Work Plan:MBI projects have specific objectives that lead to scientific accomplishments and programmatic growth through increased grant and contract activity. It is expected that all MAES-funded projects eventually become funded by extramural sources. This increased extramural funding leads to sustainable increases in graduate student and research associate numbers. Results are disseminated through published scholarly activity and various outreach activities.

Progress 10/01/19 to 09/30/20

Outputs
Target Audience:Researchers in the field of veterinary immunology, and infectious disease and medicine. Ultimate goal of many of the efforts in this project is to develop novel treatments for diseases of relevance to the livestock industry. New efforts also extend to a better understanding of the role of microbes in the environment and have the potential to have a broader impact on agriculture, in general, including impacting plant growers and soil scientists. Changes/Problems:The COVID-19 crisis was a major challenge in the past year, but faculty were able to work through many of the difficulties and continued to make progress in each of their projects. What opportunities for training and professional development has the project provided?Each faculty member supports undergraduate and graduate student research and professional development as part of the expectations of their appointments How have the results been disseminated to communities of interest?Research publications, along with presentations at scientific meetings, have served as the primary mechanism for dissemination to communities of interest. What do you plan to do during the next reporting period to accomplish the goals?Continued support will be provided to Dr. Frank Stewart as he establishes his new MAES project at MSU. The department has a number of open faculty lines, but the timeline to fill these positions is unknown due to a moratorium on hiring becasue of the COVID-19 crisis. Once approvals are given, this project will support the hiring of these new faculty as done in the past. Finally, this project will continue to support services relevant to all MAES projects in the department.

Impacts
What was accomplished under these goals? A new faculty member, Dr. Frank Stewart, started his Montana Agricultural Experiment Station (MAES) appointment in February of 2020. Dr. Stewart will be establishing a new reseach project in the department in water microbiology. The current plan is that he will prepare and submit a new MAES project application in his second year. In continuation from last year, support was provided to two new faculty in the department to aid in establishing their new MAES and Hatch projects. Dr. Rynda-Apple continued her development of a new project on respiratory diseases in domestic sheep, focused onstudies of innate and adaptive immune responses against Mycoplasma ovipneumoniae infection, and has her own approved project. Dr. Sara Branco continued her work on ectomycorrhizal fungi evolved tolerance to contaminated soils. Understanding suchphenomena is urgently needed as information on these processes will enable better predictions of the impacts ofenvironmental change and habitat degradation on plant productivity, diversity, and distribution. In addition, identifying fungia dapted to harsh environmental conditions that confer plant stress tolerance can also enable the development of tools andprotocols for expanding plant growth in sub-optimal environments. Dr. Branco prepared a new MAES/Hatch project proposal, which was reviewed and approved and submitted to USDA/NIFA for final approval. Subsequently, Dr. Branco was recruited to another institution in summer of 2020 and her project was retracted. Finally, department service efforts supported by this project contributed to efforts of the following Montana Agricultural Experiment Station faculty in the department leading to publications: Mark Quinn, Blake Wiedenheft, Edward Schmidt, Mark Jutila and Diane Bimczok.

Publications

  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Skelton RM, Shepardson KM, Hatton A, Wilson PT, Sreenivasan C, Yu J, Wang D, Huber VC, Rynda-Apple A. 2019. Contribution of host immune responses against influenza D virus infection toward secondary bacterial infection in a mouse model. Viruses 11:994.
  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Caston RR, Sierra JC, Foegeding NJ, Truelock MD, Campbell AM, Frick-Cheng AE, Bimczok D, Wilson KT, McClain MS, Cover TL.2020. Functional properties of helicobacter pylori VacA toxin m1 and m2 variants. Infection and Immunity, 88:e00032-20
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Schepetkin IA, Karpenko AS, Khlebnikov AI, Shibinska MO, Levandovskiy IA, Kirpotina LN, Danilenko NV, Quinn MT. 2019. Synthesis, anticancer activity, and molecular modeling of 1,4-napthoquinones that inhibit MKK7 and Cdc25. Eur. J. Med. Chem. 183:111719.
  • Type: Journal Articles Status: Published Year Published: 2020 Citation: D�ka �, Ida T, Dagnell M, Abiko Y, Luong NC, Balog N, Takata T, Espinosa B, Nishimura A, Cheng Q, Funato Y, Miki H, Fukuto JM, Prigge JR, Schmidt EE, Arn�r ESJ, Kumagai Y, Akaike T, Nagy P. 2020. Control of protein function through oxidation and reduction of persulfated states. Sci. Adv. 6:eaax8358.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Buyukyoruk M, Wiedenheft B. 2019. Type I-F CRISPR-Cas provides protection from DNA, but not RNA phages. Cell Disco. 5:54.
  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Cicha C, Hedges J, Novak I, Snyder D, Jutila M, Wiedenheft B. 2020. Complete genome sequence of Brucella abortus phage EF4, determined using long-read sequencing. Microbiol. Resour. Announc. 9:e00212-20


Progress 10/01/18 to 09/30/19

Outputs
Target Audience:Researchers in the field of veterinary immunology and infectious disease and medicine. Ultimate goal of most of the efforts in this project is to develop novel treatments for diseases of relevance to the livestock industry. New efforts also extend to a better understanding of the role of microbes in the environment and have the potential to have a broader impact on agriculture, in general, including impacting plant growers and soil scientists. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Each faculty member supports undergraduate and graduate student research and professional development as part of the expectations of their appointments. How have the results been disseminated to communities of interest?Research publications, along with presentations at scientific meetings, have served as the primary mechanism for dissemination to communities of interest. What do you plan to do during the next reporting period to accomplish the goals?A new faculty member who is focused on acquatic microbiology (Dr, Frank Stewart) will start in Spring, 2020 and support for his research program will be the major focus on this departmental MAES/Hatch project. A search for an additional faculty member who can contribute to efforts in Animal Health research, specifically infectious diseases in livestock, in the department is anticiapted for the coming year and this MAES/Hatch project will support those efforts.

Impacts
What was accomplished under these goals? Supported provided to two new faculty in the department to aid in establishing their new Montana Agricultural Experiment Station (MAES) and Hatch projects. A new project being led by Dr. Agnieszka Rynda-Apple is focused on respiratory diseases of relevance to animal health. Dr. Rynda-Apple has established a nationally competitive program in this area of research. Specifically, with support from this departmental project, in the past year, she developed a new project on respiratory diseases in domestic sheep, focused on studies of innate and adaptive immune responses against Mycoplasma ovipneumoniae infection. She prepared a project proposal that was eventually accepted by USDA/NIFA and which started in July, 2019. Her efforts are focused on new vaccine development for respiratory diseases of relevance to both animal and human health. Another project, which expands the impact of departmental research in micobiology, is by Dr. Sara Branco who is establshing a new research program on how ectomycorrhizal fungi evolve tolerance to contaminated soils. Understanding such phenomena is urgently needed as information on these processes will enable better predictions of the impacts of environmental change and habitat degradation on plant productivity, diversity, and distribution. In addition, identifying fungi adapted to harsh environmental conditions that confer plant stress tolerance can also enable the development of tools and protocols for expanding plant growth in sub-optimal environments. This project will also contribute to our understanding of fungal evolution in general which may be relevant to the evolution of pathogenic fungi of relevance to animal and human health. Dr. Branco has prepared a new MAES/Hatch project proposal, which will be reviewed this December and eventually submitted to USDA/NIFA for approval.

Publications

  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Shepardson K, Larson K, Cho H, Johns LL, Malkoc Z, Stanek K, Wellhman J, Zaiser S, Daggs-Olson J, Moodie T, Klonoski JM, Huber VC, Rynda-Apple A. A Novel Role for PDZ-Binding Motif of Influenza A Virus Nonstructural Protein 1 in Regulation of Host Susceptibility to Postinfluenza Bacterial Superinfections. Viral Immunol. 2019 Apr;32(3):131-143. PMID: 30822217;
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Becker DJ, Czirj�k G�, Rynda-Apple A, Plowright RK. Handling Stress and Sample Storage Are Associated with Weaker Complement-Mediated Bactericidal Ability in Birds but Not Bats. Physiol Biochem Zool. 2019 Jan/Feb;92(1):37-48 PMID: 30481115
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Shepardson KM, Larson K, Johns LL, Stanek K, Cho H, Wellham J, Henderson H, Rynda-Apple A. IFNAR2 Is Required for Anti-influenza Immunity and Alters Susceptibility to Post-influenza Bacterial Superinfections. Front Immunol. 2018 Nov 9; 9:2589


Progress 10/01/17 to 09/30/18

Outputs
Target Audience:Researchers in the field of veterinary immunology, infectious disease and medicine. Ultimate goal of efforts in this project is to develop novel treatments for diseases of relevance to the livestock industry. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Each new faculty member supports undergraduate and graduate student research and professional development as part of the expectations of their appointments. How have the results been disseminated to communities of interest?Research publications along with presentation at scientific meetings, have served as the primary mechanism for dissemination to communities of interest. What do you plan to do during the next reporting period to accomplish the goals?Continue support of new faculty as they establish projects for submission to the Montana Agricultural Experiment Station/Hatch and various federal agencies for future funding and establishment of their own indiviudal projects. Dr. Rynda-Apple and Branco will be suported through their development of MAES projects in the coming year. The department is searching for a new faculty member and he/she will also be supported by this project.

Impacts
What was accomplished under these goals? Support was provided to two new faculty in the department to establish new MAES projects: Dr. Agnieszka Rynda-Apple who is establishing a new respiratory disease research program in the department. She will submit a MAES project next year. Dr. Sara Branco who is establishing a new fungal research program in the department. She will submit a MAES/Hatch project in the next year. Continue support of ogoing MAES projects supported last year, which includes Dr. Doug Kominsky who is studying the function of the epithelium in intestinal disease, including Salmonella induced enteritis, which will be expanded into studies in bovine calves. He initiated a new MAES project this year. Dr. Diane Bimczok who has established a project on the gastric mucosa and the function of gastric dendritic cells. She is developing a new project in pigs. She initiated a new MAES project this year. Dr. Raina Plowright who has established a disease ecology research program, including work on respiratory disease in domestic and bighorn sheep. She initiated a new MAES project this year.

Publications

  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Sebrell TA, Sidar B, Bruns R, Wilkinson RA, Wiedenheft B, Taylor PJ, Perrino BA, Samuelson LC, Wilking JN, Bimczok D.Live imaging analysis of human gastric epithelial spheroids reveals spontaneous rupture, rotation and fusion events. Cell Tissue Res. 2018 Feb;371(2):293-307.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Washburne AD, Crowley DE, Becker DJ, Olival KJ, Taylor M, Munster VJ, Plowright RK. Taxonomic patterns in the zoonotic potential of mammalian viruses.PeerJ. 2018 Nov 28;6:e5979.
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2019 Citation: Becker DJ, Czirj�k G�, Rynda-Apple A, Plowright RK.Handling Stress and Sample Storage Are Associated with Weaker Complement-Mediated Bactericidal Ability in Birds but Not Bats. Physiol Biochem Zool. 2019 Jan/Feb;92(1):37-48.
  • Type: Journal Articles Status: Published Year Published: 2018 Citation: Shepardson KM, Larson K, Johns LL, Stanek K, Cho H, Wellham J, Henderson H, Rynda-Apple A. IFNAR2 Is Required for Anti-influenza Immunity and Alters Susceptibility to Post-influenza Bacterial Superinfections. Front Immunol. 2018 Nov 9;9:2589.


Progress 10/01/16 to 09/30/17

Outputs
Target Audience:Researchers focused on mucosal and pulmonary immunology in livestock, along with studies of infectious disease ecology and pathogen spillover between animal populations Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Each new faculty member supports undergraduate and graduate student research and professional development as part of the expectations of their appointments. How have the results been disseminated to communities of interest?Each new faculty member has published peer-reviewed papers in the past year on their main projects, which, along with presentation at scientific meetings, has served as the primary mechanism for dissemination to communities of interest. What do you plan to do during the next reporting period to accomplish the goals?Continue support of new faculty as they establish projects for submission to the Montana Agricultural Experiment Station and various federal agencies for future funding and establishment of their own indiviudal projects. Dr. Rynda-Apple and a new faculty member that has just started, Dr. Sara Branco, will be supported in the coming year.

Impacts
What was accomplished under these goals? Support was provided to four new faculty in the department to establish new MAES projects: Dr. Doug Kominsky who is studying the function of the epithelium in intestinal disease, including Salmonella induced enteritis, which will be exapnded into studies in bovine calves. He is submitting a MAES project this year. Dr. Diane Bimczok who has established a project on the gastric mucosa and the function of gastric dendritic cells. She is developing a new project in pigs. She is submitting a MAES project this year. Dr. Raina Plowright who has established a disease ecology research program, including work on respiratory disease in domestic and bighorn sheep. She is submitting a MAES project this year. Dr. Agnieszka Rynda-Apple who is establishing a new respiratory disease research program in the department. She will submit a MAES project next year.

Publications

  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Kelly M. Shepardson, Benjamin Schwarz, Kyle Larson, Rachelle V. Morton, John Avera, Kimberly McCoy, Alayna Caffrey, Ann Harmsen, Trevor Douglas, and Agnieszka Rynda-Apple. 2017. Induction of antiviral immune response through recognition of the repeating subunit pattern of viral capsids is toll-like receptor 2 dependent. mBio 8:e01356-17
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Sebrell TA, Sidar B, Bruns R, Wilkinson RA, Wiedenheft B, Taylor PJ, Perrino BA, Samuelson LC, Wilking JN, Bimczok D. 2017. Live imaging analysis of human gastric epithelial spheroids reveals spontaneous rupture, rotation and fusion events. Cell Tissue Res. In press
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Roe MM, Swain S, Sebrell TA, Sewell MA, Collins MM, Perrino BA, Smith PD, Smythies LE, Bimczok D. 2017. Differential regulation of CD103 (alphaE integrin) expression in human dendritic cells by retinoic acid and Toll-like receptor ligands. J. Leuk. Biol. 101:1169-1180.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Kao DJ, Saeedi BJ, Kitzenberg D, Burney KM, Dobrinskikh E, Battista KD, V�zquez-Torres A, Colgan SP, Kominsky DJ.2017. Intestinal Epithelial Ecto-5'-Nucleotidase (CD73) Regulates Intestinal Colonization and Infection by Nontyphoidal Salmonella. Infect. Immun. In press.
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Kirpotina LN, Schepetkin IA, Khlebnikov AI, Ruban OI, Ge Y, Ye RD, Kominsky DJ, Quinn MT. 2017. 4-Aroyl-3-hydroxy-5-phenyl-1H-pyrrol-2(5H)-ones as N-formyl peptide receptor 1 (FPR1) antagonists. Biochem. Pharmacol. 142:120-132
  • Type: Journal Articles Status: Published Year Published: 2017 Citation: Plowright RK, Manlove KR, Besser TE, P�ez DJ, Andrews KR, Matthews PE, Waits LP, Hudson PJ, Cassirer EF. 2017. Age-specific infectious period shapes dynamics of pneumonia in bighorn sheep. Ecol. Lett. 20:1325-1336.


Progress 07/01/16 to 09/30/16

Outputs
Target Audience:Researchers focused on mucosal and pulmonary immunology in livestock, along with studies of infectious disease ecology and pathogen spillover between animal populations. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals?All investigators supported by this project will use this support to develop research projects of direct relevance to livestock and agriculture, in general. All supported investigators have Montana Agricultural Experiment Station appointments and are expected to develop experiment station projects. An additional expectation is that the development of these projects leads to new grant applications and future funding for their work.

Impacts
What was accomplished under these goals? This is a new project initiated on 7/1/16. As such, this report only reflects accomplishments over three months. During this time, projects led by Dr. Doug Kominsky focused on salmonella infection of the intestinal mucusa, Diane Bimczok focused on studies of dendritic cells of the gastric mucosa and Helicobacter suis infection in pigs, and Raina Plowright focused on infectious disease ecology and pathogen spillover as it relates to domestic and bighorn sheep pneumonia were initiated. A new faculty member, Agnieska Rynda-Apple started her position on July 1, 2016 and is supported by this project to develop a pulmonary immunology research program focused on viral diseases of the lung. Funding is provided mainly for support of a portion of the PI's salary, but also modest support of some laboratory operations.

Publications