NEWS Despite decades of research, we still do not fully understand how some of our most widely used antibiotics kill bacteria. Now, Professor Felipe Cava at ͯÑÕÊÓƵ has received a prestigious NIH grant to solve this puzzle using new technology in close collaboration with a leading US researcher.
Professor Felipe Cava receiving the NIH fgrant highlights the strength of Umeå University’s international research environment in infection biology and the value of long-term collaboration.
ImageMattias Pettersson, simon ohman jonsson inhousebyran“It feels very rewarding. This grant builds on several years of work in my lab, particularly the development of technologies that allow us to study the bacterial cell wall in unprecedented detail,” says Felipe Cava, professor at the Department of Molecular Biology at Umeå University.
He adds:
“It also reflects a long and highly productive collaboration with Associate Professor Tobias Dörr at Cornell University, which has been central to shaping the project. We came close in a previous round, so we refined our ideas and strengthened the science. Seeing that persistence pay off is very satisfying.”
Beta-lactam antibiotics, such as penicillin, are among the most widely used treatments for bacterial infections. They target the bacterial cell wall, which is essential for survival. While we know these drugs block the enzymes that build the wall, how this ultimately leads to cell rupture remains unclear. In this project, Felipe Cava and Tobias Dörr aim to understand what happens inside the cell once wall construction is disrupted and how this process leads to cell death.
“By combining genetics, cell biology and biochemistry, we will track how the cell wall is remodelled and destabilised during treatment. We aim to build a more complete picture of how these antibiotics work,” says Felipe Cava.
The grant enables the team to tackle this challenge in ways not previously possible. A key limitation in the field has been the lack of tools to observe how the cell wall breaks down during treatment.
“In my lab, we recently developed a high‑throughput approach that changes this. For the first time, we can analyse not only intact cell wall material but also the fragments released as it is dismantled. These fragments are highly informative, as they reflect the processes that ultimately lead to bacterial lysis and death.”
This approach will now be applied at scale, in combination with genetic and systems-level analyses to map bacterial responses to antibiotics under different conditions. Beyond advancing fundamental knowledge, the work could reveal new vulnerabilities in bacterial pathogens and guide the development of improved antibiotics or compounds that enhance existing treatments, an urgent need as antimicrobial resistance continues to rise.
Felipe Cava’s collaboration with Tobias Dörr dates back to their postdoctoral days.
“We were both at Harvard around the same time. Early on, we realised we were interested in similar questions but approached them from different angles, which made collaboration a natural next step.”
Since then, their labs have co-authored numerous papers. Felipe Cava’s group focuses on the biochemical and genetic basis of cell wall structure, while Tobias Dörr’s group specialises in antibiotic mechanisms and tolerance – together linking molecular detail with broader physiological responses.
“This project is the culmination of that collaboration, with shared experiments, regular discussions and lab visits, including Tobias’s visit to Umeå in 2023 and my visit to Cornell in 2024. Interestingly, this is our first joint grant, which makes it especially meaningful.”
NIH R01 grants are among the most competitive in biomedical research, with success rates typically around 10–15%. For researchers outside the US, the bar is often even higher, as proposals must demonstrate clear added value beyond the US research landscape.
The project directly addresses antimicrobial resistance, one of the most pressing global health threats. By understanding in detail how beta-lactam antibiotics ultimately cause bacterial death – and why they sometimes fail – new strategies can be developed, including “antibiotic adjuvants” that enhance the effectiveness of existing drugs.
The grant is ca. 3M USD to share between the two researchers and it runs for five years. The project highlights the strength of Umeå University’s international research environment in infection biology and the value of long-term collaboration.
