Robert Campbell, MD - US grants

The ecology of Central Arctic remains poorly described, especially the "who eats who" world of the microscopic animals that spend their lives drifting in the water, the zooplankton. Zooplankton are eaten by fish, seabirds, and baleen whales, such as the bowhead whale, and are important members of the ocean food chain. The MOSAiC (Multidisciplinary drifting Observatory for the Study of Arctic Climate) project is a unique chance to investigate these understudied animals (zooplankton) over all four seasons of the year. Here is proposed to participate in the MOSAiC expedition with an international science team to study how the biology and environment of the Arctic affect the zooplankton, to understand their role in the ecosystem (for example, who do they eat and how much), and to describe how changes in the Arctic environment, such as loss of sea ice, may affect their survival. Broader Impacts: This understanding is needed to predict how environmental change might be changing the whole Arctic ecosystem from plankton to fish to seals to humans and if the unique ice-dependent ecosystem will still remain. There have been few year-long studies of the biology of the Arctic Ocean because it is very difficult to get there during the dark, long, cold winter. The PIs will reach out to some of our youngest audiences, K-3 students at North Falmouth MA Elementary, to share our fascination with the Arctic and to introduce the students to the planktonic world and to life and work on board a ship frozen into the ice. Substantial public outreach for the project will be led by the international MOSAiC team. A postdoctoral researcher and undergraduate students will also participate in the research.

This proposal focuses on the planktonic lower trophic levels and will quantify the role that the mesozooplankton play in biological transformation and cycling of important elements (C, N) in the central Arctic Ocean ecosystem. Working together with an international team of scientists, the PIs will determine seasonal patterns in abundance, biomass, vertical distribution, and life stage structure for the entire zooplankton community using plankton nets and acoustic and optical methods. Key biological rate processes of important species will be measured experimentally to determine seasonal changes in food web dynamics and to better understand life cycle and survival strategies and how they are linked to production cycle timing. Trophic linkages will be determined using both isotopic ratios and molecular techniques. These rate processes and linkages then will be interpreted in the context of the abundance and distribution patterns, of the physical ocean environment, of sea ice quality and extent, and of season. Greater temporal and spatial context will be quantified through collaborations with MOSAiC modeling efforts. This study is novel in that it would result in the first quantification of the planktonic food web dynamics in the central Arctic through direct measurement of the important biological rate processes and will utilize both traditional and modern techniques to describe and quantify trophic linkages and carbon 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.

PROJECT SUMMARY/ABSTRACT Aging is accompanied by a decreased tolerance to physiological stress, which promotes increased susceptibility to inflammatory illnesses. Critical illnesses such as sepsis, disportionately effect people over the age of 65, leading to increased morbidity and mortality in older adults. Thrombosis is a common complication from sepsis, contributing to organ failure and death. The significance of this devastating dysregulated host response is demonstrated by data showing half of all hospital intensive care admissions are from individuals over the age of 65 and may be attributed to infection. Emerging evidence supports the concept that dysregulated platelet functions mediate the injurious host response during inflammation. Nevertheless, the molecular mechanisms and functional consequences of dysregulated platelet functions during aging and inflammation remain incompletely understood. Our proposal, entitled ?Interferon-Induced Transmembrane Protein 3 (IFITM3) Regulates Thrombosis During Inflammation in Aging? will identify new pathways by which inflammatory agonists, including interferons (IFNs), regulate gene expression in platelets and their parent cell, the megakaryocyte (MK), in aging. Our preliminary studies have identified that the expression of IFITM3 is robustly induced in human platelets during sepsis, a systemic inflammatory illness. Interestingly, MKs and platelets from aged human and mice express more IFITM3 after IFN stimulation compared to younger controls. Our data suggest that IFITM3 promotes fibrinogen endocytosis in MKs and platelets, leading to platelet hyperreactivity and thrombosis. Our findings also suggest that in aging and during inflammatory stress, the mammalian target of rapamycin pathway is activated, triggering IFITM3 synthesis and thrombosis. The expression and function of IFITM3 in MKs and platelets and its regulation by mTOR is a pathway not previously examined. In this proposal, we will couple studies in older and younger septic patients with in vitro and in vivo murine models using aged mice. These complementary human and murine studies will allow us to establish clinical relevance, while also dissecting the mechanisms by which IFITM3 governs MK and platelet function during inflammation. These studies are translational and innovative as IFITM3 regulation of endocytosis, a process critical for cellular function, has not previously been studied in MKs, platelets, or ? for that matter - any primary human cells. They will also determine for the first time whether aging alters the effect of inflammatory agonists on transcriptional and translational events in MKs and platelets. This work will test an important functional hypothesis and clarify pathophysiologic mechanisms of thrombosis aging during inflammation. This proposal has translational potential for older patients with sepsis, and also will uncover new pathways linking thrombosis and inflammation in aging.