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<jats:p> An organizing principle of the diverse cell types in multicellular organisms is their anatomic location. In turn, anatomic location is patterned by the positional identities of cells along developmental axes. Recent progress in functional genomics and chromatin biology illustrates how cells use specific gene expression programs to encode location. Dynamic chromatin states of key genes, notably the <jats:italic>Hox</jats:italic> loci, serve as the internal representation in cells of their positional identity within the animal. </jats:p>

<jats:p>The protein actin forms filaments that provide cells with mechanical support and driving forces for movement. Actin contributes to biological processes such as sensing environmental forces, internalizing membrane vesicles, moving over surfaces, and dividing the cell in two. These cellular activities are complex; they depend on interactions of actin monomers and filaments with numerous other proteins. Here, we present a summary of the key questions in the field and suggest how those questions might be answered. Understanding actin-based biological phenomena will depend on identifying the participating molecules and defining their molecular mechanisms. Comparisons of quantitative measurements of reactions in live cells with computer simulations of mathematical models will also help generate meaningful insights.</jats:p>

<jats:p>Subcellular localization of messenger RNAs (mRNAs) can give precise control over where protein products are synthesized and operate. However, just 10 years ago many in the broader cell biology community would have considered this a specialized mechanism restricted to a very small fraction of transcripts. Since then, it has become clear that subcellular targeting of mRNAs is prevalent, and there is mounting evidence for central roles for this process in many cellular events. Here, we review current knowledge of the mechanisms and functions of mRNA localization in animal cells.</jats:p>

<jats:p>The extracellular matrix (ECM) and ECM proteins are important in phenomena as diverse as developmental patterning, stem cell niches, cancer, and genetic diseases. The ECM has many effects beyond providing structural support. ECM proteins typically include multiple, independently folded domains whose sequences and arrangement are highly conserved. Some of these domains bind adhesion receptors such as integrins that mediate cell-matrix adhesion and also transduce signals into cells. However, ECM proteins also bind soluble growth factors and regulate their distribution, activation, and presentation to cells. As organized, solid-phase ligands, ECM proteins can integrate complex, multivalent signals to cells in a spatially patterned and regulated fashion. These properties need to be incorporated into considerations of the functions of the ECM.</jats:p>

<jats:p>Signal transduction can be defined as the coordinated relay of messages derived from extracellular cues to intracellular effectors. More simply put, information received on the cell surface is processed across the plasma membrane and transmitted to intracellular targets. This requires that the activators, effectors, enzymes, and substrates that respond to cellular signals come together when they need to.</jats:p>

<jats:p>Despite their small size, bacteria have a remarkably intricate internal organization. Bacteria deploy proteins and protein complexes to particular locations and do so in a dynamic manner in lockstep with the organized deployment of their chromosome. The dynamic subcellular localization of protein complexes is an integral feature of regulatory processes of bacterial cells.</jats:p>

<jats:p>Androgen signaling facilitates the formation of an oncogenic fusion gene in prostate cancer cells.</jats:p>

<jats:title>“Haploid Human”</jats:title> <jats:p> Genetic screens can provide direct insight into biological processes that are poorly understood. <jats:bold> Carette <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1231" related-article-type="in-this-issue" vol="326" xlink:href="10.1126/science.1178955">1231</jats:related-article> ) describe genetic screens using large-scale gene disruption in human cells haploid for all chromosomes except for chromosome 8. One screen was used to identify host factors essential for the activity of cytolethal distending toxin, a toxin found in several pathogenic bacteria. Another screen identified host gene products essential for infection with influenza, and an additional screen revealed genes required for the action of adenosine 5′-diphosphate (ADP)–ribosylating bacterial toxins. This loss-of-function genetic approach in mammalian cells will be widely applicable to study a variety of biological processes and cellular functions. </jats:p>

<jats:title> Simply <jats:italic>Mycoplasma</jats:italic> </jats:title> <jats:p> The bacterium <jats:italic>Mycoplasma pneumoniae</jats:italic> , a human pathogen, has a genome of reduced size and is one of the simplest organisms that can reproduce outside of host cells. As such, it represents an excellent model organism in which to attempt a systems-level understanding of its biological organization. Now three papers provide a comprehensive and quantitative analysis of the proteome, the metabolic network, and the transcriptome of <jats:italic>M. pneumoniae</jats:italic> (see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="5957" page="1200" related-article-type="in-this-issue" vol="326" xlink:href="10.1126/science.1183757">Ochman and Raghavan</jats:related-article> </jats:bold> ). Anticipating what might be possible in the future for more complex organisms, <jats:bold> Kühner <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1235" related-article-type="in-this-issue" vol="326" xlink:href="10.1126/science.1176343">1235</jats:related-article> ) combine analysis of protein interactions by mass spectrometry with extensive structural information on <jats:italic>M. pneumoniae</jats:italic> proteins to reveal how proteins work together as molecular machines and map their organization within the cell by electron tomography. The manageable genome size of <jats:italic>M. pneumoniae</jats:italic> allowed <jats:bold> Yus <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1263" related-article-type="in-this-issue" vol="326" xlink:href="10.1126/science.1177263">1263</jats:related-article> ) to map the metabolic network of the organism manually and validate it experimentally. Analysis of the network aided development of a minimal medium in which the bacterium could be cultured. Finally, <jats:bold> G‡ell <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1268" related-article-type="in-this-issue" vol="326" xlink:href="10.1126/science.1176951">1268</jats:related-article> ) applied state-of-the-art sequencing techniques to reveal that this “simple” organism makes extensive use of noncoding RNAs and has exon- and intron-like structure within transcriptional operons that allows complex gene regulation resembling that of eukaryotes. </jats:p>