Brian Geiss Gets Number 9,206,412

Brian Geiss, along with two co-workers, recently received US patent 9,206,412 for their discovery of the antiviral activity of a new class of inhibitors that bind to and inhibit flavivirus NS5 guanylyltransferase function.  This was the first class of antiviral inhibitors identified that specifically interfere with the formation of the viral RNA cap structure. 

Infectious Disease Research and Response Network (IDR2N) Designated as a CSU Program of Research and Scholarly Excellence

We are pleased to announce that the IDR2N is one of 21 newly designated Programs in Research and Scholarly Excellence (PRSE) by the Office of the Vice President for Research.  The IDR2N consists of 62 faculty from seven departments, the lion’s share of which reside in MIP.  The goals of the IDR2N are to build upon the extensive infectious disease research foundation already in place at CSU and (1) enhance the response of CSU infectious disease research community to opportunities, (2) establish effective clinical collaborations, (3) promote state-of-the-art research and research infrastructure, and (4) expand infectious disease research training opportunities.  Congratulations to John Belisle who spearheaded the effort to create the IDR2N and we look forward to exciting times ahead!

Kendra Andrie hails from Muskegon, Michigan and will be in the Anatomic Pathology Program. She is interested in researching infectious disease, with a particular interest in virology. In her spare time Kendra enjoys hiking, biking, ice hockey, spending time with her boyfriend and their dog Ruby.

Mike Betley will also be part of the Anatomic Pathology Program.  Mike is from Saint Louis in the ‘Show Me’ State of Missouri and is interested in neuropathology and cancer. In his free time he enjoys cycling, hiking and skiing.

Broomfield, Colorado native Samantha McDonnel will be in the Clinical Pathology Program.   She is interested in researching comparative virology and gene therapy. In her free time she enjoys running, planning her wedding and helping with feral cat clinics.

Brian Smith will be part of our Comparative Medicine Program. Brian is from Sacramento, California and is interested in laboratory animal medicine. Biking, hiking, kayaking, playing soccer and disc golf are his interests outside of the lab.

Anatomic Pathology resident Benjamin Curtis is from Grand Rapids, Michigan and is interested in researching diagnostic development. In his spare time he enjoys camping, biking, running, watching sports, spending time with his wife Abby and his new son Grayson (pictured elsewhere in this newsletter).

In the News...

Reyes Featured in Coloradoan

MIP Grad Student Reyes Murrieta was featured in a video for the Coloradoan about the first West Nile Virus case that was confirmed in Fort Collins. Check out the video here

Rebekah Kading:  TV Star and Rift Valley Fever Researcher

Channel 7 recently aired a story on surveillance efforts for Rift Valley Fever Virus-infected mosquitoes starring Dr. Kading and crew.

Check it out here.

At Olympics' start, Zika funding at CSU hits impasse

Grag Ebel was quoted in a Coloradoan article about the Zika virus and funding at CSU to research it.

Check it out here.

Zabel Figure Makes the Cover of Prion

Artwork submitted by the Zabel lab recently made the cover of Prion to highlight their recent paper in the lab (which by the way was the MIPub of the Month for June….)

Check it out here.

Assembling of the Mycobacterium tuberculosis Cell Wall Core

Anna Grzegorzewicz, , Celia de Sousa-d'Auria, Mike McNeil, Emilie Huc-Claustre, Victoria Jones, Cecile Petit, Shiva Angala, Julia Zemanová, Qinglan Wang, Juan Belardinelli, Qian Gao, Yoshimasa Ishizaki, Katarina Mikušová, Pat Brennan, Donald Ronning, Mohamed Chami, Christine Houssin, and Mary Jackson

Journal of Biological Chemistry, In Press (July 14, 2016)

From Donald Trump to Mycobacteria, seems like everyone these days wants to build a wall.  The trick of course, is how to do it effectively (and of course who will pay for it).  While we don’t have any answers for Mr. Trump’s wall, this paper by Anna et al provides a pretty interesting clue to how mycobacteria effectively wall themselves off from their neighbors.

Building a mycobacterial cell wall requires several key steps – and one of the most important ones is covalently linking the fundamental peptidoglycan (PG) component to the arabinogalactan (AG) moieties that allow the external wall components to be effectively assembled.  However the enzyme that’s responsible for this important ‘PG-AG’ linkage has been a puzzling question for many years.  Our MRL team, along with their international collaborators, came up with an interesting hypothesis to address this knowledge gap.  Other Gram positive bacteria use enzymes from the LCP family of proteins to attach things to their peptidoglycans – and Mycobacteria possess three LCP family homologs.  Not only that, but knocking out a LCP protein in Corynebacteria leads to clear cell wall assembly defects. Could one or more of these three mycobacteria LCP homologs be the culprits that attach AG to PG? 

The team stopped hypothesizing and started experimenting, using a series of biochemical and genetic assays to find out.  Three pieces of evidence convinced them that the Mycobacteria ‘CpsA1 and A2’ genes are key architects of the mycobacteria membrane core.  First, the CpsA1 and A2 proteins are found precisely on the membrane where they would need to be to attach AG to PG.  Second, recombinantly produced CpsA1 and A2 proteins act as Mg-dependent pyrophosphatases, which is precisely the enzymatic activity they would need to mediate PG-AG attachment.  Finally, while knocking out both proteins is lethal, knocking out CpsA1 causes growth defects as well as membrane cording defects in certain mycobacaterial genetic backgrounds.  Therefore despite the lack of a definitive assay to easily assess LCP protein function in mycobacteria, these three lines of evidence provide a strong indication that CpsA1 and CpsA2 are very likely the enzymes involved in AG attachment to PG.

So why did we choose this study as our MIPublication of the Month© for July?  First, given that many of our most effective antibiotics target bacterial cell wall synthesis, the identification of CpsA1/A2 as key cell wall enzymes in Mycobacteria tuberculosis is obviously a big deal.  In fact, inactivating the CpsA1 protein in Mtb makes it much more susceptible to a variety of known antibiotics – perhaps due to a flimsy, hypersensitive cell wall that is constructed in the absence of the LCP protein.  Second, this paper is authored by not only three faculty/ laboratories in the CSU-MRL, but also has collaborators from five other countries on two other continents. The study is thus a poster child of synergy and international cooperation – in fact there are co-first authors (Anna and Celia) as well as co-senior authors (Mary and Christine).  Finally, with the Rio Olympics track and field events to begin shortly, we wanted to make sure we picked a paper that was fast – and this paper is ‘acid’ fast…….

MIP Publications June 2016

Ruple A, Avery AC, Morley PS.  Differences in the geographic distribution of lymphoma subtypes in Golden retrievers in the USA.  Vet Comp Oncol. 2016 Jul 27. doi: 10.1111/vco.12258.

Rotcheewaphan S, Belisle JT, Webb KJ, Kim HJ, Spencer JS, Borlee BR.  Diguanylate cyclase activity of the Mycobacterium leprae T cell antigen ML1419c.  Microbiology. 2016 Jul 22. doi: 10.1099/mic.0.000339.

Schenk M, Mahapatra S, Le P, Kim HJ, Choi AW, Brennan PJ, Belisle JT, Modlin RL.  Human NOD2 Recognizes Structurally Unique Muramyl Dipeptides from Mycobacterium leprae.  Infect Immun. 2016 Jun 13. pii: IAI.00334-16

Grzegorzewicz AE, De Sousa-d'Auria C, McNeil MR, Huc-Claustre E, Jones V, Petit C, Angala SK, Zemanová J, Wang Q, Belardinelli JM, Gao Q, Ishizaki Y, Mikušová K, Brennan PJ, Ronning DR, Chami M, Houssin C, Jackson M.  Assembling of the Mycobacterium tuberculosis Cell Wall Core.  J Biol Chem. 2016 Jul 14. pii: jbc.M116.739227

Xia M, Hesser DC, De P, Sakala IG, Spencer CT, Kirkwood JS, Abate G, Chatterjee D, Dobos KM, Hoft DF.  A Subset of Protective γ9δ2 T cells is Activated by Novel Mycobacterial Lipid Components.  Infect Immun. 2016 Jun 13. pii: IAI.01322-15.

Curtis RC, Custis JT, Ehrhart NP, Ehrhart EJ, Condon KW, Gookin SE, Donahue SW.  Combination Therapy with Zoledronic Acid and Parathyroid Hormone Improves Bone Architecture and Strength following a Clinically-Relevant Dose of Stereotactic Radiation Therapy for the Local Treatment of Canine Osteosarcoma in Athymic Rats.  PLoS One. 2016 Jun 22;11(6):e0158005. doi: 10.1371/journal.pone.0158005.

Bullard-Feibelman KM, Fuller BP, Geiss BJ.  A Sensitive and Robust High-Throughput Screening Assay for Inhibitors of the Chikungunya Virus nsP1 Capping Enzyme.  PLoS One. 2016 Jul 18;11(7):e0158923. doi: 10.1371/journal.pone.0158923.

Li W, Obregón-Henao A, Wallach JB, North EJ, Lee RE, Gonzalez-Juarrero M, Schnappinger D, Jackson M.  Therapeutic potential of the Mycobacterium tuberculosis mycolic acid transporter, MmpL3.  Antimicrob Agents Chemother. 2016 Jun 13. pii: AAC.00826-16.

Lozano-Fuentes S, Kading RC, Hartman DA, Okoth E, Githaka N, Nene V, Poché RM.  Evaluation of a topical formulation of eprinomectin against Anopheles arabiensis when administered to Zebu cattle (Bos indicus) under field conditions.  Malar J. 2016 Jun 17;15:324. doi: 10.1186/s12936-016-1361-z.

Lehman SS, Mladinich KM, Boonyakanog A, Mima T, Karkhoff-Schweizer RR, Schweizer HP.  Versatile nourseothricin and streptomycin/spectinomycin resistance gene cassettes and their use in chromosome integration vectors.  J Microbiol Methods. 2016 Jul 22. pii: S0167-7012(16)30190-7. doi: 10.1016/j.mimet.2016.07.018.

Miller MR, McMinn RJ, Misra V, Schountz T, Müller MA, Kurth A, Munster VJ.  Broad and Temperature Independent Replication Potential of Filoviruses on Cells Derived From Old and New World Bat Species.  J Infect Dis. 2016 Jun 26. pii: jiw199.

Salgado CG, Barreto JG, da Silva MB, Frade MA, Spencer JS. What do we actually know about leprosy worldwide?
Lancet Infect Dis. 2016 Jul;16(7):778. doi: 10.1016/S1473-3099(16)30090-1.

Pokeman Go – Gotta Catch ‘em All

Pokemon were spotted in the Wilusz lab on the 3rd Floor of the Microbiology Bldg

Did you know that the Pathology Building is a Pokemon gym?????

The Graduate Student Organization Wants to Take You Out to the Ballgame

What: Colorado Rockies Game

When: August 16, 6:40pm (Tuesday)

How: Drive yourself or carpool with us, leaving CSU 5:15-5:30pm

Cost: $10 per ticket

Who: MIP, plus friends or family

Reserve your ticket here BY NOON on MONDAY, AUGUST 1. The GSO will be in touch about distributing tickets and carpooling.

Jeff Wilusz recently (got photobombed) and caught a foul ball hit by the Twins Eduardo Nunez while seated in the right field pavilion seats behind first base in Fenway Park. 

What are Graduates of our Micro MS-B Program up to now?

The Micro MS-B Program has been up and running for three years now and boasts a graduation rate of 100%!   However the true measure of a program’s success is what its graduates accomplish.  Here’s what some of our MS-B graduates are currently doing:

Cassie Zych: vet tech at Thompson Animal Hospital.

Carl Dernell: Attending CU Medical School (Class of 2019).

Lauren Tauer: Microbiologist at Accuratus Lab Services.

Aja Norman: Will enter CSU Vet School this Fall.

Mike Mangalea: PhD Student in Borlee lab.

Delaney Swindle: Researching ovarian function in relation to fat diets at UC Denver.

Erin Massey: Scientist at BioMarc.

Marshall Henderson: Attending St. George Medical School this Fall.

Isabella Mazariegos: Microbiologist at New Belgium Brewing Co.

Hannah Clark: Quality Control Analyst for MedImmune.

Kristine Breivik: Quality Control Analyst at Tolmar.

Jordan Flatt: Manufacturing Associate at BioMARC.

Mariah Pippins: Screening Lab Technician at Cordant Health Soluations.

Paul Burns: Researcher at CDC.

Andy Gonzalez: PhD graduate student at University of Idaho.

Grady Gray: Attending Vet School at Arizona Midwestern University.

Daria Malishkin: Attending CSU Vet School (class of 2020).

Bobby Onaga: Attending Vet School at Cornell.

Katie Sonsteng: Professional Research Associate at Anschutz Medical Campus.

Brie Nixon: Interning at Tolmar.

Jessica Cole: PhD Program with Brian Geiss.

Rosie Horst: Lab Scientist at Denver Health.

Christy Martinez: Pharmacy Technician at North Suburban Medical Center.

Meghin Kiernan: Attending CSU Vet School this Fall.

Dayton Pierce: PhD program at CSU- Cell and Molecular Biology.

Lauren Eytalis: Attending CSU Vet School this Fall. 

Megan Morris: Attending Vet School at St. George University.

Brooke Plumley: Working in Brad Borlee's Lab.

Joe Guy: Research Lab Technician at the University of Michigan.

Ralph Smith Captures Nature at its Best

Check out his beautiful photo of a trio of columbines taken by MIP Professor emeritus Ralph Smith during the Crested Butte Wildflower Festival. 

Mark your Calendar! Rocky Mountain Virology Club- 16th Annual Meeting

The annual Rocky Mountain Virology Club Meeting, scheduled for September 23-25th at Pingree Park, is now less than two months away!   Registration is open so don’t be left out.   Information on the meeting, including the 9 invited speakers, can be found here.

Drinking Tecates and Posin’ for Pictures Once Upon a Time in Mexico Gerry Callahan, circa 1975

This ~ 1975 photo of a group from the Scripps Clinic and Research Foundation (La Jolla, CA) was taken in a drinking establishment in Tijuana, Mexico. Left rear is Joe Palca, a research tech at the time who is now an NPR Science Correspondent, seated next to the woman he was dating at the time.  Right front is Gerry Callahan (yes, believe it or not with hair) from his postdoctoral days.  Right middle is a postdoc named James P. Allison – who received the 2015 Lasker Award and is considered a possible future Nobel Laureate for his pioneering work in T cell immunology.  Right rear is Jim’s first wife Melinda Allison. 

One Health:  Vet Resident Does UCHSC Lab Rotation

Anna Fagre spent three weeks at CU Health shadowing physicians and technicians in the Clinical Microbiology Lab. She attended rounds with all of the residents and internists three times a week and went through a self-guided set of unknowns. This was a great way to extend one’s diagnostic training by learning how a high-throughput human microbiology lab is run.

Vet Diagnostic Lab Lines

Check out the latest edition of Lab Lines here

Guest Blog for Scientific American

Anna Fagre had her guest blog, Why Don't Bats Get Ebola? published for Scientific America. Check out the blog here.

Parking permits expire on July 31st. Make sure to renew them if you plan to park on campus.

Get more informatino here.

Ben Curtis and his wife Abby welcomed their first son, Grayson, into the world on July 4th, 2016.

Talent hits the target that can’t be hit.
Genius hits the target that can’t be seen.
Wisdom knows what targets should actually be hit.

-Ansler Schopenhopin

Choose your Caption

Jeff Wilusz was interviewed by Portuguese TV during the late night celebrations in downtown Lisbon Portugal following the victory by the national team in EuroCup 2016

Alternative captions:

1. Best thing on TV from New Jersey since Snooki and Jersey Shore

2. Wilusz shamelessly borrows a move from Fonzie and Siskel & Ebert

3. Having no ability to understand Portuguese, Jeff nevertheless responds to a question regarding his opinion of the Republican Candidate for President

4.Proof that unlike MIPnews readers, intoxicated Portuguese think inane puns are really funny

5. Submit your own

"Should our accountants be forgot, and never brought to mind ? Should HR, front desk, travel, and other programmatic staff be forgot, and old lang syne ?"

As we welcome in another CSU Fiscal New Year on July 1st, let's not forget to thank the hard working staff who create the docs, push the paper and coordinate the oftentimes behind-the-scenes effort that make our MIP-world tick. You guys and gals are the ‘Dream Team’ of CSU office staff.

Official CSU Holiday List for FY ‘17

• Monday, July 4, 2016
• Monday, September 5, 2016
• Thursday, November 24, 2016
• Friday, November 25, 2016
• Monday, December 26, 2016
• Tuesday, December 27, 2016
• Wednesday, December 28, 2016
• Monday, January 2, 2017
• Monday, January 16, 2017
• Monday, May 29, 2017

NIH-sponsored Educational Loan Repayment Programs for researchers with direct pediatric relevance

Got ideas on how to improve graduate education?  NIH wants to know about them

NIGMS recently issued a request for information (RFI) on ‘Strategies for Modernizing Biomedical Graduate Education’.  If you have any thoughts regarding the current strengths/challenges in graduate education, changes that could enhance the experience for students, and major barriers to achieve these needed changes – please visit https://www.research.net/r/Graduate_Education by August 5th and share your thoughts with NIH. 

New Grant Awards

Brad Borlee, "Pathogen Activated Antimicrobial Devices", Colo Office of Economic Dev & Intl Trade.

Ed Hoover, "Project 3: CWD Prion Shedding and Environmental Contamination: Role in Transmission and Zoonotic Potential", University of Texas Health Science Center. "Biomedical Research Training for Veterinarians", HHS-NIH-National Institutes of Health.

Glenn Telling, " Core B: Science Core in Pathogenesis, Transmission and Detection of Zoonotic Prion Diseases (P01),"University of Texas Health Science Center. "Project 1: Modeling the Mechanisms of Prion Transmission, Strain Selection, Mutation and Species Barrier in Transgenic Mice", University of Texas Health Science Center.

John Belisle, "CD1-Restricted T-Cell Responses in Skin", University of California, Los Angeles.

Ken Olson, "Task Order Request C03: "Efficacy Study for Nootkatone as Insecticidal Agent against Mosquitoes Harboring Arboviruses (including ZIKV)", HHS-NIH-NIAID-Allergy & Infect Diseases.

Rebekah Kading, "Arthropod-borne Viruses Associated with the Chiroptera of Uganda: Isolation and Characterization", HHS-CDC-Centers for Disease Control.

Sandra Quackenbush, "Molecular Biology Services for Wildlife Disease Diagnostics", Colorado Division of Parks and Wildlife.

Steven Dow, "Genetic Risk Alleles as Drivers of Loss of Anergic B Cells in Autoimmunity", HHS-NIH-National Institutes of Health.

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