Candidates in Our Backyard

New UMBC-led research in Frontiers in Microbiology suggests that viruses are using information from their environment to “decide” when to sit tight inside their hosts and when to multiply and burst out, killing the host cell. The work has implications for antiviral drug development.

A virus’s ability to sense its environment, including elements produced by its host, adds “another layer of complexity to the viral-host interaction,” says Ivan Erill, professor of biological sciences and senior author on the new paper. Right now, viruses are exploiting that ability to their benefit. But in the future, he says, “we could exploit it to their detriment.”

Not a coincidence

The new study focused on bacteriophages—viruses that infect bacteria, often referred to simply as “phages.” The phages in the study can only infect their hosts when the bacterial cells have special appendages, called pili and flagella, that help the bacteria move and mate. The bacteria produce a protein called CtrA that controls when they generate these appendages. The new paper shows that many appendage-dependent phages have patterns in their DNA where the CtrA protein can attach, called binding sites. A phage having a binding site for a protein produced by its host is unusual, Erill says.

Even more surprising, Erill and the paper’s first author Elia Mascolo, a Ph.D. student in Erill’s lab, found through detailed genomic analysis that these binding sites were not unique to a single phage, or even a single group of phages. Many different types of phages had CtrA binding sites—but they all required their hosts to have pili and/or flagella to infect them. It couldn’t be a coincidence, they decided.

The ability to monitor CtrA levels “has been invented multiple times throughout evolution by different phages that infect different bacteria,” Erill says. When distantly related species demonstrate a similar trait, it’s called convergent evolution—and it indicates that the trait is definitely useful.

Timing is everything

Another wrinkle in the story: The first phage in which the research team identified CtrA binding sites infects a particular group of bacteria called Caulobacterales. Caulobacterales are an especially well-studied group of bacteria, because they exist in two forms: a “swarmer” form that swims around freely, and a “stalked” form that attaches to a surface. The swarmers have pili/flagella, and the stalks do not. In these bacteria, CtrA also regulates the cell cycle, determining whether a cell will divide evenly into two more of the same cell type, or divide asymmetrically to produce one swarmer and one stalk cell.

Because the phages can only infect swarmer cells, it’s in their best interest only to burst out of their host when there are many swarmer cells available to infect. Generally, Caulobacterales live in nutrient-poor environments, and they are very spread out. “But when they find a good pocket of microhabitat, they become stalked cells and proliferate,” Erill says, eventually producing large quantities of swarmer cells.

So, “We hypothesize the phages are monitoring CtrA levels, which go up and down during the life cycle of the cells, to figure out when the swarmer cell is becoming a stalk cell and becoming a factory of swarmers,” Erill says, “and at that point, they burst the cell, because there are going to be many swarmers nearby to infect.”

Listening in

Unfortunately, the method to prove this hypothesis is labor-intensive and extremely difficult, so that wasn’t part of this latest paper—although Erill and colleagues hope to tackle that question in the future. However, the research team sees no other plausible explanation for the proliferation of CtrA binding sites on so many different phages, all of which require pili/flagella to infect their hosts. Even more interesting, they note, are the implications for viruses that infect other organisms—even humans.

“Everything that we know about phages, every single evolutionary strategy they have developed, has been shown to translate to viruses that infect plants and animals,” he says. “It’s almost a given. So if phages are listening in on their hosts, the viruses that affect humans are bound to be doing the same.”

There are a few other documented examples of phages monitoring their environment in interesting ways, but none include so many different phages employing the same strategy against so many bacterial hosts.

This new research is the “first broad scope demonstration that phages are listening in on what’s going on in the cell, in this case, in terms of cell development,” Erill says. But more examples are on the way, he predicts. Already, members of his lab have started looking for receptors for other bacterial regulatory molecules in phages, he says—and they’re finding them.

New therapeutic avenues

The key takeaway from this research is that “the virus is using cellular intel to make decisions,” Erill says, “and if it’s happening in bacteria, it’s almost certainly happening in plants and animals, because if it’s an evolutionary strategy that makes sense, evolution will discover it and exploit it.”

For example, to optimize its strategy for survival and replication, an animal virus might want to know what kind of tissue it is in, or how robust the host’s immune response is to its infection. While it might be unsettling to think about all the information viruses could gather and possibly use to make us sicker, these discoveries also open up avenues for new therapies.

“If you are developing an antiviral drug, and you know the virus is listening in on a particular signal, then maybe you can fool the virus,” Erill says. That’s several steps away, however. For now, “We are just starting to realize how actively viruses have eyes on us—how they are monitoring what’s going on around them and making decisions based on that,” Erill says. “It’s fascinating.”

Financial Conflict of Interest (FCOI) and Other Support: Reminders

Notice Number:  NOT-OD-22-210

Purpose:

The purpose of this Guide Notice is twofold: (1) to remind the NIH extramural research community about the longstanding requirements provided in the financial conflict of interest (FCOI) regulation at 42 CFR Part 50 Subpart F, “Promoting Objectivity in Research” (FCOI regulation for grants and cooperative agreements). This requirement also is included in the NIH Grants Policy Statement (NIH GPS), Section 4.1.10, Financial Conflict of Interest, and serves as a term and condition of NIH grant awards. This Notice reminds the extramural applicants and recipient institutions of the requirements to develop a FCOI policy, to post it on their website and submit it to NIH, to ensure Investigator disclosure of both foreign and domestic Significant Financial Interests(SFI), to review Investigator SFIs, to determine if there is a FCOI that must be reported to NIH, and to train Investigators on FCOI requirements; and (2) to remind the NIH extramural research community of the requirement to submit complete and accurate Other Support information (NOT-OD-21-073) (NOT-OD-21-110).

Please refer to the full notice linked below for further details.

https://grants.nih.gov/grants/guide/notice-files/NOT-OD-22-210.html

Should you have any questions, please contact the Office of Sponsored Programs.

UMBC and the University of Maryland School of Medicine (UMSOM) have received a five-year, $13.7 million grant from the National Institutes of Health (NIH) to enhance recruitment and training of junior faculty from groups underrepresented in biomedical science. Funding is through the NIH Common Fund Faculty Institutional Recruitment for Sustainable Transformation (FIRST) program, which was founded last year to support efforts to hire groups of diverse, early-career research faculty. 

The grant will enable the universities to hire a group of four faculty members at UMBC and six at UMSOM, each of whom will have cross-campus appointments at both institutions. 

“Faculty hired under UM-FIRST will advance our teaching and research missions and serve as leaders for institutional change as we pursue our vision of a diverse professoriate,” says William LaCourse, dean of the College of Natural and Mathematical Sciences and professor of chemistry and biochemistry at UMBC. “These faculty and those who follow will also serve as role models for future generations of underrepresented students.”

Fostering culture change

The grant aims to build self-reinforcing communities of scientists committed to diversity and inclusive excellence through the recruitment of early-career faculty who are competitive for assistant professor positions and have demonstrated commitment to promoting diversity and inclusion. UMSOM and UMBC will measure their progress against clearly defined metrics of institutional culture change, diversity, and inclusion to determine if hiring efforts and other evidence-based strategies are achieving the program’s goals. 

The grant “is designed to foster sustainable culture change and promote inclusive excellence by enabling us to hire a diverse cohort of new faculty and to support faculty development, mentoring, and promotion opportunities,” says James Kaper, the lead on the grant and the James and Carolyn Frenkil Distinguished Dean’s Professor, vice dean for Academic Affairs, and chair of microbiology and immunology at UMSOM.

Building on a legacy of inclusion

The NIH FIRST grant builds on UMBC’s highly esteemed Meyerhoff Scholars Program, launched more than 30 years ago, which has led UMBC to become a leading university for developing underrepresented STEM undergraduates. UMBC is now the nation’s number #1 producer of Black undergraduates who go on to complete a PhD in the natural sciences or engineering and #1 for Black undergraduates who complete an M.D./Ph.D. 

At the same time that UMBC excels in educating undergraduates, the university is also classified as one of only 146 R1 (“very high research activity”) institutions in the nation.

UMBC’s efforts to promote faculty diversity in STEM include the PROMISE Academy and ADVANCE, which has increased women faculty in STEM by 70 percent at UMBC since 2003. 

The College of Natural and Mathematical Sciences’ Pre-professoriate Fellowship offers incoming faculty two-year appointments as research assistant professors, with structured mentoring and other scaffolds for success. Faculty who came to UMBC through this program in biological sciences, physics, and chemistry have already been converted to tenure-track assistant professors. 

Unwavering dedication

The recent $10M INCLUDES grant awarded to UMBC further builds a robust, diverse pipeline in STEM at UMBC by supporting postdocs from underrepresented groups, and the PROMISE Allegiance for Graduate Education and the Professoriate (AGEP) program offers professional development and community to all graduate students and postdocs at UMBC and throughout the University System of Maryland. 

UMSOM’s efforts to promote a diverse STEM and health-science pipeline include the UMB CURES program for middle and high school students, several internship and summer research programs for college students, and multiple post-graduate training programs that give underrepresented minority scholars direct experience in a laboratory setting.

Like many of these other initiatives, “The true strength of UM-FIRST,” LaCourse says, “ is in the unwavering dedication of the leadership, faculty, and staff of these two institutions to inclusive excellence and social justice.”

A huge thanks to the Retriever Essentials Team for holding an info session on SNAP.

• Click the Link here for the recording of the session on Wednesday 9/21

• Click here for a Link to the slides from the presentation

• Interested in signing up  for Thursday 9/29 SNAP Office Hours (1:00 to 4:00 pm @ PUP Lobby) Follow the Link

As always if you don't qualify for SNAP please visit Retriever Essentials in the Essential Space located in RAC 235 or at one of the Food Zones on Campus