ACS Infectious Diseases and the ACS Division of Biological Chemistry are proud to announce the winners of the 2017 ACS Infectious Diseases Young Investigator Awards. This year’s honors, which recognize three outstanding young investigators in the field of infectious diseases, are awarded to:

• Catherine Leimkuhler Grimes, Assistant Professor, Department of Chemistry and Biochemistry, University of Delaware
• Chao Shan, Postdoctoral Fellow, Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston
• William M. Wuest, GRA Distinguished Investigator and Acting Associate Professor, Chemistry, Emory University

As winners of the 2017 ACS Infectious Diseases Young Investigator Awards, Grimes, Shan, and Wuest each will receive a plaque, an award of $1,000, and up to $500 in travel reimbursement to attend the 2017 ACS Fall National Meeting in Washington, D.C., and present at an ACS Division of Biological Chemistry symposium in their honor. The journal and the Division encourage you to attend the ACS Infectious Diseases Young Investigator Awards Symposium Wednesday, August 23, from 8:30 a.m. to 11 a.m. in Room 145B of the Walter E. Washington Convention Center.

To learn more about these great young investigators, I reached out to ACS Infectious Diseases Editor-in-Chief Courtney C. Aldrich for more information about why each was selected for this award. I also connected with the winners to learn more about their research. Read on to find out what they said.

Catherine Leimkuhler Grimes

“Dr. Catherine Leimkuhler Grimes has done foundational work at the interface of chemistry, microbiology, and immunology to decipher the molecular interactions between bacteria and our immune system,” Aldrich said. “A greater understanding of how our immune system recognizes bacteria could result in a paradigm shift in addressing antimicrobial resistance.”

Read all of Grimes’s ACS Publications-published research here and read on to learn more about her work.

How did you get into studying immune response?

As a graduate student, working with Professor Daniel Kahne, we investigated the problem of glycopeptides resistance. Glycopeptides, such as vancomycin, inhibit the biosynthesis of the polymer, peptidoglycan which serves as a protective shield for the bacteria. I began to read about how the human immune system, independent of an antibiotic, use defined fragments of the peptidoglycan to generate an innate response. As a post-doctoral fellow, working with Professors Erin K. O’Shea and Daniel K. Podolsky, I learned about the important signaling mechanisms that the human immune systems uses to respond to these fragments. Now, in my own laboratory at University of Delaware, we combine carbohydrate chemistry and biochemistry with molecular and microbiology to determine normal and disease sensing of the innate immune response.

What’s the most exciting discovery you’ve made in your career so far?

My laboratory has determined that NOD2, an innate immune protein that is mutated in Crohn’s disease, is highly unstable in the cellular environment. We have established biochemical assays, which rely on carbohydrate chemistry to determine that this protein binds directly to bacterial peptidoglycan fragments and is truly an innate immune receptor.

What’s next in your research?

We are very interested in determining the biologically relevant fragments of peptidoglycan (PG) from commensal and pathogenic bacteria. We have recently developed a methodology to metabolically install bio-orthogonal probes into the glycan backbone of the PG, allowing us to track and capture the reactive fragments in a variety of settings.

In addition, my lab is developing high throughput methods to screen for small molecule stabilizers of NOD2, as we have established that the molecular chaperone, Hsp70, is capable of rescuing the Crohn’s associated phenotype.

Is there anything else you’d like to share?

I am extremely grateful to all of my mentors and collaborators, especially my students at the University of Delaware for believing in me. Finally, I would like to thank Professor Jack Strominger for providing an incredible foundation to the field of bacterial peptidoglycans and who once told me “with love and desire you can do anything”.

Chao Shan

“Dr. Chao Shan has successfully developed the first reverse-genetic system for Zika virus. The system has made it feasible to study the molecular biology of Zika epidemic/disease and to develop countermeasures (vaccine and therapeutics),” said Aldrich. “This system has been widely shared and used by many research groups around the world. The development of such experimental system represents a major breakthrough in Zika virus research.”

Read Shan’s ACS Infectious Diseases-published research here and read on to learn more about his work.

How did you get into studying Zika virus?

I joined Dr. Pei-Yong Shi’s group as a postdoctoral fellow in December 2015 when Zika virus (ZIKV) became epidemic in the Americas. Since our group is good at reversing the genetic system of Flavivirus and the system is urgently needed for ZIKV research, I am mainly working to develop a ZIKV reverse genetic system.

What’s the most exciting discovery you’ve made in your career so far?

I built the first ZIKV reverse genetic system in the world and it has been widely used by many research groups. And based on this reverse genetic system, I have developed the first live-attenuated Zika vaccine candidate which showed sterilizing immunity in both mouse and non-human primate models while preventing pregnancy transmission and testis damage.

What’s next in your research?

In the future, I would like to further characterize vaccine candidates and explore why ZIKV caused this epidemic.

Is there anything else you’d like to share?

I would like to thank each of our lab members and all of our great collaborators, especially my mentor Dr. Shi for all his support during this period. Research is really moving very fast in the Zika field. I couldn’t achieve these discoveries without help from the UTMB community and awesome collaborators from other universities. Thank you for all the support and suggestions for my research.

William M. Wuest

“Dr. William M. Wuest has established a world-renowned research program focused on studying and perturbing bacterial biofilms with small molecules using an innovative combination of chemical biology, medicinal chemistry, and diverted total synthesis. His review on the development and resistance of quaternary ammonium compounds – “Quaternary Ammonium Compounds: An Antimicrobial Mainstay and Platform for Innovation to Address Bacterial Resistance” – remains the most-cited paper in ACS Infectious Diseases.

Wuest’s ACS Publications-published research here and read on to learn more about his work.

How did you get into studying natural products with a focus on combating bacterial biofilms?

Ever since I was a graduate student, I have been fascinated by natural products and their role in medicine. Therefore, it seemed logical to make them the focus of my initial job proposals; however, I wanted to expand into an area that both differed from my training and was lacking a critical mass of synthetic chemists. After discussions with my postdoc advisor, Chris Walsh, I realized that bacterial biofilms was exactly the place to launch my career.

What’s the most exciting discovery you’ve made in your career so far?

That’s a tough question! I would say that our work investigating quaternary ammonium compound (QAC)-resistance (or as I like to describe it, “how Methicillin-resistant Staphylococcus aureus can fight Lysol”) is probably our most influential. However, I am partial to our work on the natural product promysalin, a Pseudomonad-specific antibiotic, which provided the first synthesis, structural assignment, interesting biological activity, and most recently the biological target of the compound and mode of action, as it continues to push our understanding of how nature evolves small molecules to be both potent and selective.

What’s next in your research?

With my group’s recent move to Emory University, I felt that this would be an ideal time to expand our research focus beyond bacterial biofilms and look into other areas antibacterial research. More specifically, we are looking to expand our “narrow-spectrum” research program with a focus on Pseudomonad-specific therapies in collaboration with the CF-Atlanta group. Likewise, we also plan to work closely with the Antibiotic Resistance Center here at Emory to further investigate mechanisms of antibiotic resistance development by both using our current, and continuing to develop, chemical probes.

Is there anything else you’d like to share?

I would like to express my appreciation to the chemical biology community, and more specifically the chemists working in the infectious disease field. Their continual support of our program and words of encouragement throughout the pre-tenure process have been invaluable and I look forward to paying it forward to future junior faculty. Finally, none of these discoveries would have been possible without the hard work and dedication of my entire group (@WuestLab) who continually strive to Do Better both in the lab and in the community!