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, 2010), nitrogen cycling (Beman et?al., 2007; Siboni et?al., 2008; Olson et?al., 2009), or pathogen survival (Looney et?al., 2010). A parallel continuum of size must be layered into our understanding as organic matter, the fuel for heterotrophic microbial processes, is considered within the spatial continuum of the reef environment. One of the next challenges for the field is to elucidate and quantify the mechanistic connections among these microbial communities within this multidimensional, multi-scale framework to attain a cause-and-effect understanding of how a reef ecosystem functions. The technology is now available to begin adding multiple spatial and time scale contexts PI3K activation to fundamental questions of coral reef ecosystem function such as how growth of associated microbial communities is regulated, why Tryptophan synthase we see certain dominances in a given niche, what the primary sources of bacterial mortality are under specific environmental conditions, and how all of these mechanisms relate to the health or disease state of a reef (see Fig.?3). For example, new developments in confocal imaging technology have enabled the visualization of the natural coral�Cmicrobial assemblage in situ, and micro-scale ecological interactions can now be observed in real time (M. Garren and F. Azam, submitted). As we consider questions that are currently driving the field of coral microbial ecology forward, it is an opportune moment to reflect on the progress that has been made in recent history. In 2003, Knowlton and Rohwer wrote an article in The American Naturalist entitled ��Multispecies microbial Alectinib solubility dmso mutualisms on coral reefs: the host as a habitat�� (Knowlton and Rohwer, 2003). They outlined the then most current understanding of bacterial and archaeal associations with corals, and concluded that ��we know almost nothing about the role of non-eukaryotic microbes in healthy coral�� (p. S54). Among the research questions that they suggested to drive the field forward were: (i) What is the scope of diversity for coral-associated bacteria and archaea, and how is it patterned in space and time? (ii) Which of the many bacterial and archaeal associates of corals are true mutualists, and what roles do they play? (iii) How important are bacterial and archaeal communities to the health of coral reefs, and are they being disrupted by anthropogenic stress? The field has made substantial progress on these questions in the past 8 years, and yet there remains much to be learned by revisiting these same questions and taking advantage of significant advances in genomics and imaging technologies. As discussed earlier and recently reviewed by others (Bourne et?al., 2009; Ainsworth et?al., 2010; Mouchka et?al., 2010), the scope of diversity of bacteria is much clearer than it was before, and we have more information about patterns of distribution and diversity through space and time.