Swarts Lab

12/30/2019: Research highlights from 2019

A few highlight publications from the past year:

11/15/2019: Sabbatical dispatch

On sabbatical for the 2019-2020 academic year, Ben made stops at Colorado State University Mycobacteria Research Laboratories (MRL) and Wadsworth Center Mycobacteriology Labs (Albany, NY) to meet with collaborators, present seminars, and tour TB research and diagnostic facilities. In addition, gave a talk at the ACS National Meeting in San Diego, attended the 15th MCGS at the University of Notre Dame, and gave a keynote talk at the Kalamzoo ACS section meeting, held at Bell's Brewery in Kalamazoo, MI. Students joined to present their research for all three meetings.

07/08/2019: Collaborative paper

Temitope Nathan contributed to a paper from the Eoh lab (University of Southern California): J. J. Lee, S.-K. Lee, N. Song, T. O. Nathan, B. M. Swarts, S. Y. Eum, S. Ehrt, S.-N. Cho, H. Eoh*. Transient drug-tolerance and permanent drug-resistance rely on the trehalose-catalytic shift in Mycobacterium tuberculosis, Nat. Commun. 2019, 10, 2928.

06/08/2019: 50th CERM in Midland, MI

The 50th ACS Central Regional Meeting was held down the road in Midland, MI. Ben co-organized a chemical biology symposium with CMU colleague Dr. Lin Zhao, and numerous students from the lab presented their research, including Alicyn, Dan, Qing Qing, Justin, Kyle, and Nicholas.

05/28/2019: New community college outreach participants

Welcome to Hamzah Khan and Kaitlyn Viaene, the two newest participants in our community college summer research outreach program, which is now in its 5th year. Both Hamzah and Kaitlyn are from Delta College.

04/10/2019: New paper in Chem. Commun.

"Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile" was published in Chem. Commun. This study, carried out in collaboration with Dr. Robert Britton at Baylor College of Medicine, describes trehalase-resistant trehalose analogues as the first inhibitors of hypervirulence-associated trehalose metabolism in the intestinal pathogen Clostridioides difficile.

04/10/2019: Collaborative paper

Alicyn Stothard contributed to a paper from the DeBosch lab (Washington University St. Louis, School of Medicine): Y. Zhang, C. B. Higgins, H. M. Fortune, P. Chen, A. I. Stothard, A. L. Mayer, B. M. Swarts, B. J. DeBosch*. Hepatic Arginase 2 (Arg2) is sufficient to convey the therapeutic metabolic effects of fasting. Nat. Commun. 2019, 10, 1587.

02/27/2019: New paper in ACS Omega

"A FRET-based fluorogenic trehalose dimycolate analogue for probing mycomembrane-remodeling enzymes of mycobacteria" was published in ACS Omega. This study was started by Claudia Ramsey, carried on by Nate Holmes and Herbert Kavunja, and contributed to by a number of others, including collaborators from Toledo and University at Albany. It involves the development and evaluation of a fluorogenic glycolipid probe that can report in real time on activity from enzymes involved in remodeling of the mycobacterial outer membrane.

01/15/2019: Welcome new student

Biochemistry major Blake Holdwick has joined the team.

12/27/2018: New paper in ChemBioChem

"Engineering the mycomembrane of live mycobacteria with an expanded set of trehalose monomycolate analogues" was published in ChemBioChem. This paper, led by Taylor Fiolek and Nicholas Banahene, describes a toolbox of probe compounds that can integrate into the mycomembrane of living mycobacterial cells to enable detection or cell surface engineering applications.

11/05/2018: New paper in Carbohydr. Res.

"Chemoenzymatic radiosynthesis of 2-deoxy-2-[18F]fluoro-d-trehalose ([18F]-2-FDTre): A PET radioprobe for in vivo tracing of trehalose metabolism" was published in Carbohydrate Research. This was a collaboration between our lab and Prof. Juan Vaquero's group at UC3M (Madrid, Spain). The paper reports a rapid, one-step radiosynthesis of 18F-trehalose, which may of be future interest for selective in vivo PET imaging of bacterial infections. We collaborated with SOFIE Biosciences to automate the radiosynthesis on their ELIXYS platform.

10/26/2018: Dreyfus Teacher-Scholar Symposium

Ben presented a poster, "Illuminating the Mycobacterial Cell Wall through Undergraduate Chemical Biology Research," at the 2018 Dreyfus Foundation Teacher-Scholar Symposium in New York City. As part of the Henry Dreyfus Teacher-Scholar award, the group put together a short video about our research with the help of CMU University Communications. See chemistry research videos from other Teacher-Scholars at the Dreyfus Foundation website.

10/13/2018: Fall conferences

Our students presented their research at the 14th annual Midwest Carbohydrate & Glycobiology Symposium (MCGS), this year organized by Prof. Xuefei Huang at Michigan State University, as well as at the ACS Midland Fall Scientific Meeting. Presenters included Nicholas Banahene, Alex Ausmus, Alicyn Stothard, Dan Gepford, and Dillon Vannest. Congratulations to Alicyn, who won Best Poster Awards at both meetings.

10/01/2018: M.S. thesis defenses, new students

Congratulations to Nicholas Banahene and Doug Wing on successfully defending their M.S. theses! Next, Nicholas will remain at CMU, entering the BCMB Ph.D. program, while Doug is off to work as an analytical chemist at Eurofins Lancaster (CT). Best wishes to Doug, who was one of the first students to join the lab as a CMU undergraduate student back in 2013.

We also welcome two new graduate students and three new undergraduate students. Karishma Kalera (B.Sc, M.Sc.) is a microbiologist who will be studying here in the BCMB Ph.D. program under the support of a predoctoral graduate fellowship from the Government of India, Ministry of Social Justice and Empowerment. Abi Detlzer was a CMU undergraduate who graduated in May 2018 and will continue at CMU in the Chemistry M.S. program. New undergraduate students include Justin Snyder, who transferred to CMU after visiting us from MCC over the summer, as well as Isaac Angera and Madison Saunders.

09/10/2018: Collaborative papers

Taylor Fiolek and Sarah Rundell contributed to a paper from the Siegrist lab (UMass-Amherst, Department of Microbiology) and Alicyn Stothard contributed to a paper from the DeBosch lab (Washington University St. Louis, School of Medicine):

• • C. B. Higgins, Y. Zhang, H. Fujiwara, A. L. Mayer, M. J. Graham, A. I. Stothard, B. M. Swarts, and B. J. DeBosch*. Hepatocyte ALOXE3 is induced during the murine adaptive fasting response and enhances insulin sensitivity by activating hepatic PPAR-gamma. JCI Insight, 2018, DOI: 10.1172/jci.insight.120794

  • A. Heredia-García, A. A. Pohane, E. Melzer, C. R. Carr, T. J. Fiolek, S. R. Rundell, H. Chuin Lim, J. C. Wagner, Y. S. Morita, E. J. Rubin, B. M. Swarts, and M. S. Siegrist*. Peptidoglycan precursor synthesis along the sidewall of pole-growing mycobacteria, eLife, 2018, e37243.

07/05/2018: New paper in J. Org. Chem.

"Chemoenzymatic synthesis of trehalosamine, an aminoglycoside antibiotic and precursor to mycobacterial imaging probes" was published in the Journal of Organic Chemistry. This work was led by undergraduate student Jessica Groenevelt and describes a concise route to the natural product trehalosamine, which exhibits good antimicrobial activity against Mycobacterium tuberculosis.

05/01/2018: Good luck to numerous graduating students

A number of our undergraduate students are part of CMU's class of 2018, and we wish them congratulations on all of their hard work and good luck! Abigail Detzler (B.S. Biochemistry) will enter the Chemistry M.S. program at CMU, Nate Holmes (B.S. Biomedical Sciences, CMU Summer Scholar, CMU Honors Program) will start medical school at Michigan State University, Jeff Wolber (B.S. Neuroscience) will start medical school at the University of Michigan, Jessica Groenevelt (B.S. Biochemistry) will start a Chemistry Ph.D. at Wayne State University, Mara O'Neill (B.S. Chemistry) will seek a position in industry, Devin Moore (B.S. Biochemistry, McNair Scholar) will be doing clinical work in a gap year before medical school, and Noah Danielson (B.S. Biochemistry, CMU Honors Program) will start a Biochemistry Ph.D. at Purdue University.

Several of these students have won awards, including Jessica (2 best poster awards), Nate (CMU Provost's Award for Undergrad Research), and Noah (CMU Dept of Chemistry Outstanding Undergraduate Researcher and ACS Midland Section Outstanding Senior Biochemistry Major).

01/20/2018: Welcome new students

Welcome to new undergraduate students Nikolas Kambitsis and Cameron Lee, both biochemistry majors.

09/15/2017: Thesis defense, new students

Congratulations to Taylor Fiolek on an excellent M.S. thesis defense in late August--good luck in the chemistry Ph.D. program at Michigan State University! As Taylor leaves, we welcome Qing Qing Dong and Alex Ausmus, who are students in the chemistry M.S. program. Also, following their stints in the lab over the summer, both Dan and Dillon will continue working in the lab as CMU biochemistry majors.

08/09/2017: New paper in Carbohydr. Res.

"The trehalose-specific transporter LpqY-SugABC is required for antimicrobial and anti-biofilm activity of trehalose analogues in Mycobacterium smegmatis" has been published in Carbohydrate Research. This paper, led by undergraduates Jeff Wolber and Bailey Urbanek, identifies trehalose analogues as metabolically-driven inhibitors of mycobacterial biofilm formation.

08/09/2017: Dreyfus grant

Ben received the Henry Dreyfus Teacher-Scholar Award from the Camille and Henry Dreyfus Foundation. This award supports the research and teaching careers of chemistry faculty working with undergraduate students.

06/29/2017: Collaborative paper

Max Hogue contributed to a paper from the Boyce lab (Duke University, School of Medicine):

• • P.-H. Chen, T. J. Smith, J. Wu, P. F. Siesser, F. Khan, M. Hogue, E. Soderblom, F. Tang, J. R. Marks, M. B. Major, B. M. Swarts, M. Boyce,* and J.-T. Chi*. Glycosylation of KEAP1 links nutrient sensing to redox stress signaling, EMBO J. 2017, DOI: 10.15252/embj.201696113.

05/04/2017: NSF CAREER grant

We have been generously funded by the NSF with a CAREER Award to support our project focused on developing new tools to investigate the composition and dynamics of the mycobacterial outer membrane.

05/01/2017: Good luck graduates

Congratulations to the undergraduate students in the group who are graduating in the CMU class of 2017! Brent Piligian has been in the lab since 2014 and will graduate with a B.S. in Biomedical Sciences before going to the NIH for a postbaccalaureate research internship. Adrian Rylski joined the group in early 2015 and will graduate with a B.S. degree in Biochemistry, then start an internship at Dow Chemical. Claudia Ramsey has been in the lab since late 2015 and will graduate with a B.S. in Biomedical Sciences prior to starting med school at the Medical College of Wisconsin. Tina Bednarz also joined the group in late 2015. She will receive her B.S. degree in Biochemistry and begin at the University of Michigan PharmD program. We will miss you all, good luck!

02/21/2017: Video protocol in J. Vis. Exp.

Lisa Meints's paper, "Rapid one-step enzymatic synthesis and all-aqueous purification of trehalose analogues," has been published in the Journal of Visualized Experiments. This work, which is an extension of our previously published TreT-catalyzed synthesis of trehalose analogues, includes a detailed video protocol for obtaining TreT and using it to easily produce trehalose analogues. Much of this work was completed by Lisa Meints, while Brent Piligian performed the protocol on camera.

01/13/2017: Review article in Pure & Applied Chemistry

"Tailoring trehalose for biomedical and biotechnological applications" has been published in Pure Appl. Chem. This review article was heavily contributed to by undergraduate students Mara O'Neill and Brent Piligian. It covers chemical and chemoenzymatic approaches to trehalose analogue synthesis, as well as applications of trehalose analogues in various fields.