Uncovering Ancient Immune Strategies to Solve Modern Antimicrobial Resistance Challenges
Dr. Benjamin Morehouse studies a unique branch of immunology called “ancient immunity.” Like an archeologist searching for clues among ancient ruins, Morehouse scours the ancient genomes of bacteria for yet undiscovered immune treasures. These hidden treasures hold the key to novel antimicrobial agents that target the immune system rather than the pathogen, opening the door to therapies with the potential to treat both bacterial and viral infections with less risk for antimicrobial resistance.
“Our lab aims to establish commonalities in immunity that are conserved across living organisms, to identify features we share with bacteria in how we sense and respond to pathogens. By exploring immune systems of diverse organisms, we can uncover new strategies for immune defense,” says Morehouse. Using this approach, his team recently identified a novel protein called SIRal that is central in triggering innate immune defenses against both bacteria and viruses. The discovery has the potential to reshape how we fight infection.
What makes SIRal especially unique is how it seems to function. Rather than acting as a direct pathogen sensor, it appears to be more like a central adapter or command hub that translates danger signals into coordinated immune action. That positioning could be powerful: targeting a central immune node may offer broad protection against diverse bacterial or viral threats with a single drug. In addition, the approach would avoid resistance issues that arise when drugs target the evasive pathogens themselves.
“It's motivating from an antimicrobial resistance angle,” says Morehouse. “We need new strategies to prevent infections and overcome resistance problems. Conventional antibiotic approaches are not succeeding and actually doing more harm than good lately.” Indeed, antimicrobial resistance is classified as one of the top 10 global public health threats facing humanity today, according to the World Health Organization.
The first step to realizing this potential is to learn exactly how SIRa1 operates. Morehouse will use the 2026 Michelson Prizes: Next Generation Grants funds to understand how SIRal drives immune responses by defining the protein structure, identifying interacting partners and categorizing downstream signals, all of which will provide clues as to how to target the protein therapeutically. “We're here to identify phenomena, then clinicians can build upon our descriptions and medicinal chemists can develop drugs to target these systems. Without knowing the nature of the systems, it would be impossible to target them for therapeutic benefit.” This is the essential, but often hidden, role that basic research plays in enabling medical advances that the Michelson Medical Research Foundation aims to support.
By investing in this project, the impacts could extend far beyond infectious disease treatments. In fact, drugs targeting SIRa1 could be powerful across a broad spectrum of diseases including cancer, autoimmune, and autoinflammatory diseases. Agonists that activate SIRal could boost immune responses against cancer cells, while antagonists that shut down SIRal activity might quell overactive inflammation in IBS or inflammatory skin diseases. Along these lines, Morehouse is collaborating with an interdisciplinary team of bioinformaticians, clinicians, immunologists, and cell biologists to study genetic mutations in SIRal that are found in patients with inflammatory conditions. They hope to categorize these mutations and explore how they may be aberrantly ramping up inflammation in these disease states. “I love being in this interdisciplinary space because it recruits really interesting people from different directions, bringing creativity to the work,” he says.
Morehouse himself comes from a multidisciplinary background, which inspires his own creativity. Where others see boundaries between fields, Morehouse sees bridges and derives unique insights at these intersections. “Initially as a grad student I wanted to collect as many skills as possible. Over time, I realized the real value in this was being able to speak the languages of different scientific areas and make connections between them that other people don't make. I've studied ion transporters in pancreatic cancer (undergrad), plant natural product biosynthesis and fungal cyclic nucleotide signaling (grad school), and immunology/microbiology (postdoc). Being trained in many fields allows me to speak different scientific languages, making our research more interdisciplinary, which I think leads to more effective outcomes.”
This background aligns perfectly with the Michelson Medical Research Foundation’s philosophy that innovation and breakthroughs in immunology and immunotherapy require many disparate perspectives and non-traditional ideas, which is why interdisciplinary teams and scientists from diverse disciplines are encouraged to apply for the Michelson Prizes, and often win!
Morehouse credits his successes to his students, and for someone just three years into his faculty career, has demonstrated a remarkable propensity for mentorship. “When deciding where to establish my lab, I wanted to be at an undergraduate-focused institution. They bring infinite optimism and youthful energy that fuels the rest of the lab,” he says. The Morehouse lab is running on high octane when it comes to youthful energy, with a total of 15 trainees, more than half of whom are undergraduates. For Morehouse, this next generation of scientists isn’t an afterthought, it’s the heartbeat of the research and his career. “They come in with eyes wide open, and keeping them that way, keeping them excited about science, is my job. Seeing the spark of discovery in my trainees, and their excitement about probing the depths of what’s out there in immune signaling, makes this job worth it.”
