This project studied the response of keystone marine cyanobacteria such as Trichodesmium, Synechococcus, and Prochlorococcus to multiple stressors. The study observed selection by high CO2 treatments during long-term experimental evolution experiment resulting in a constitutive increase in nitrogen fixation rates. This observation showed that this cyanobacterium could become "stuck" with elevated N2 fixation rates in the future ocean conditions, even after return to pre-industrial conditions. This outcome has consequences for ocean biology and biogeochemistry, including those connected to iron and phosphorus limitation of new production in marine ecosystems if enhanced productivity continues. Further this study examined the influence of co-limitation by iron and phosphorus, two nutrients that can both be so low as to constrain productivity in the oceans. In these experiments a co-limited phenotype was discovered that was unique from single limitation, implying that multiple stressors have their own unique response as opposed to being additive independent responses. Iron scarcity experiments were conducted on coastal and open ocean Synechococcus that revealed a highly dynamic response in coastal isolates implying conditions of iron scarcity are far more important than previously recognized. Zinc toxicity studies were also conducted on the abundant cyanobacterium Prochlorococcus, revealing that Pacific isolates can extraordinarily susceptible to zinc toxicity likely due to lack of exposure in that region. Finally a review of two component regulatory systems, which contribute to the key control switches within bacteria, found that marine microbes have significantly different ratios of their two component systems compared to previously characterized organisms. This deviance is likely due to the extreme scarcity of nutrients and the need to conserve nitrogen and phosphate in protein and DNA involved in maintaining these control systems. Finally this project contributed to the development of a novel "targeted metaproteomic" method to allow direct absolute and high-throughput measurement of proteins in natural environments. Overall, this project furthered knowledge regarding the influence of key nutrients and micronutrients on abundant phytoplankton in the ocean. Last Modified: 07/17/2018 Submitted by: Mak A Saito