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TTU Ph.D. alumnus Urvish Trivedi

Alumnus Urvish Trivedi Receives Danish Research Grant

Biochemistry Grad Will Use 'Trojan Horses' to Intercept Microbial Communications and Combat Pathogens

11.22.2019

Alumnus Urvish Trivedi, Ph.D. (TTU, B.Sc. Biochemistry, 2011; University of Copenhagen, Ph.D. Microbiology, 2018), a postdoctoral fellow at the University of Copenhagen in Denmark and former TTU/Howard Hughes Medical Institute undergraduate research scholar, recently was awarded his first independent research grant.

Trivedi is one of 52 selected from 449 applicants to receive funding from the Velux Foundations' Villum Experiment, which supports unorthodox ideas that are high-risk/high-gain. Trivedi's award of $266,831 over two years is to study "Surveillance of microbial small talk using Trojan horses."

The Language of Microbes

Until recently, it was believed that microorganisms lived independent, unicellular lives. It is now understood that they rely on complex systems of social behaviors for survival, and that includes communication.

Trivedi's research focuses on the social lives of microbes and host-pathogen interactions. He says that bacteria communicate with one another using chemical signaling molecules as words.

"They release, detect, and respond to the accumulation of these molecules through a process called quorum sensing (QS). The QS signals allow bacteria to synchronously control gene expression of an entire community in response to changes in cell density and species complexity," Trivedi says. "Many behaviors are regulated by QS, including toxin production, foraging, virulence, symbiosis, and mating. That is how, in brief, one can picture how QS allows bacteria to behave collectively as multicellular organisms and reap benefits that would otherwise be unattainable to them as individuals, similar in principle to a school of fish or swarm of insects."

Trivedi continues: "Curiously, there are also highly specific QS languages that enable bacteria to communicate within species. The advantage of having species-specific signals is that it prevents bacteria from being confused by noise; it allows them to keep their conversations private, i.e. within their own species; and modulate group behavior with tight specificity. This ensures that only those that possess a cognate receptor and recognize the specific QS signal will perform the signal-dependent response (e.g. coordinated release of toxins). However, such a high level of specificity can be exploited to identify and target bacteria. Therefore, in terms of microbial warfare, there is a possibility to engineer a synthetic system that can intercept species-specific signals to coordinately target a bacterial population and use their own arsenal against them."

Where the Trojan Horses Comes In

Trivedi's Villium Experiment project, "Surveillance of microbial small talk using Trojan horses," aims to engineer and characterize a library of synthetic "Trojan horses" that can target bacteria based on species-specific communication signals or molecular/cellular structures. The key questions to be addressed include how to intercept signals made by target bacteria to deliver target-specific phage and toxins, and how to activate and control such a system with high specificity.

"This experiment can open brand-new avenues and cause a paradigm shift in favor of using synthetic biology as part of future antimicrobial strategies," Trivedi says. "There is an urgent need for new alternative ways to target bacteria; however, the prospect of using synthetic constructs is still relatively unexplored. A Trojan horse that seeks out its targets in order to eliminate them seems like a futuristic idea of microbial warfare. However, we have previously shown that bacteria are able to sense cellular structures of other competing species located nearby and use them as molecular cues to upregulate lytic activity against prokaryotic and eukaryotic cells."

"Proving how social behaviors can be exploited by synthetic constructs," Trivedi says, "will hopefully address a huge global concern—lowering antibiotic usage as part of the fight against multi-drug resistant bacteria."

Trivedi anticipates a research framework of two to three years. Within this time he expects to provide a reliable and systematic model for constructing a library of novel Trojan horses, which will be an asset for researchers everywhere. "It will give them the molecular tool kits with interchangeable biological parts needed to construct their own Trojan horses for synthetic biology-driven strategies," he says.

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About the Villum Experiment

The Villum Experiment is a unique grant in the sense that it funds radical and innovative research projects that challenge norms and have the potential to fundamentally alter the approach to important topics in science and technology. The applications reviewed are anonymous, making it a unique process because it allows research ideas to be judged on their stand-alone merit and not on the CV of the applicant. Its goal is to give unorthodox ideas the chance to become reality—bold ideas that may challenge acclaimed research but that one might not dare to mention aloud because it doesn't fit into the conventional peer-review funding system.

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