NSF-BSF: Cell death, metabolism and the emergency of long-term survival through microbial interactions in Prochlorococcus, a globally abundant marine model cyanobacterium

This project aims to understand the death of microbial cells due to nutrient starvation - a fundamental yet complex process in biology. This is crucial as microbes and their molecular processes significantly impact the broader ecosystem, with major implications for biogeochemistry and Earth’s climate. When microbial cells die, they release molecules that may feed other organisms or persist in the environment as robust organic matter. In this research project, the investigators will focus on cell death of Prochlorococcus, a widespread marine photosynthetic microbe critical to oceanic biogeochemical cycles, and whose mortality is poorly understood. The proposed research will combine innovative computational modelling and laboratory experiments to examine the intricate interplay between cellular metabolism and cell death, the fate of cellular biomass after death, and how interactions between Prochlorococcus and other bacteria affect Prochlorococcus mortality. The results of this research will help illuminate the fate of organic matter in the ocean, contributing to our understanding of oceanic dynamics, with implications for addressing global challenges such as emerging diseases and environmental sustainability. Furthermore, the project, with its integrated approach bridging biology, biochemistry, physics, and ecology, paves the way for cutting-edge interdisciplinary research. Beyond the immediate scientific impact, the endeavor will foster scientific literacy among students. In particular, the project will develop an exploration-focused, web- and field-based educational program, that introduces key concepts in microbiology, environmental sciences and oceanography to intermediate- and high-school students from low-income backgrounds, with the goal of helping them pursue successful higher education in STEM. When microbial cells die, their biomass is released, fueling growth of other organisms, or remaining in the ecosystem as long-lasting, recalcitrant organic matter. In turn, metabolic interactions with co-occurring organisms can alleviate nutrient starvation, reducing mortality. While much is known about the mechanisms employed by some model organisms to reduce nutrient stress and delay mortality, the process of cell death itself remains a “black box”. Specifically, little is known about how reduction of flux through specific metabolic pathways induces the loss of cell viability. Moreover, it is still unclear how microbial interactions can help reduce mortality and promote the emergent resilience of microbial ecosystems. The project will integrate genome-scale metabolic modelling and laboratory experiments, including flux analysis, using the abundant marine cyanobacterium Prochlorococcus and two heterotrophic partners – Alteromonas and Roseovarius. The three major questions to be addressed are: (i) What are the metabolic conditions leading to cell death?; (ii) What is the fate of cell biomass as the cells die?; and, (iii) What are the metabolic interactions with some heterotrophs (Alteromonas) but not others (Roseovarius) that reduce Prochlorococcus mortality? Key to the research project is the development of new mathematical formulations of extreme starvation and death within genome-scale, flux balance analysis (FBA) models. The models will then be validated experimentally, through detailed measurements of the physiology of the cells, their biochemical composition and turnover, gene expression and key intracellular and cell-environment fluxes of macromolecules and metabolites. This project will shed light on an important part of an organism's life cycle, cell death, and the fate and turnover of organic matter, which has major implications for biogeochemical cycling. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.