Extracellular ATP Limits Homeostatic T Cell Migration Within Lymph Nodes

Whereas adenosine 5'-triphosphate (ATP) is the major energy source in cells, extracellular ATP (eATP) released from activated/damaged cells is widely thought to represent a potent damage-associated molecular pattern that promotes inflammatory responses. Here, we provide suggestive evidence that eATP is constitutively produced in the uninflamed lymph node (LN) paracortex by naïve T cells responding to C-C chemokine receptor type 7 (CCR7) ligand chemokines. Consistently, eATP was markedly reduced in naïve T cell-depleted LNs, including those of nude mice, CCR7-deficient mice, and mice subjected to the interruption of the afferent lymphatics in local LNs. Stimulation with a CCR7 ligand chemokine, CCL19, induced ATP release from LN cells, which inhibited CCR7-dependent lymphocyte migration in vitro by a mechanism dependent on the purinoreceptor P2X7 (P2X7R), and P2X7R inhibition enhanced T cell retention in LNs in vivo. These results collectively indicate that paracortical eATP is produced by naïve T cells in response to constitutively expressed chemokines, and that eATP negatively regulates CCR7-mediated lymphocyte migration within LNs via a specific subtype of ATP receptor, demonstrating its fine-tuning role in homeostatic cell migration within LNs

The Primarily Undergraduate Nanomaterials Cooperative: A New Model for Supporting Collaborative Research at Small Institutions on a National Scale

The Primarily Undergraduate Nanomaterials Cooperative (PUNC) is an organization for research-active faculty studying nanomaterials at Primarily Undergraduate Institutions (PUIs), where undergraduate teaching and research go hand-in-hand. In this perspective, we outline the differences in maintaining an active research group at a PUI compared to an R1 institution. We also discuss the work of PUNC, which focuses on community building, instrument sharing, and facilitating new collaborations. Currently consisting of 37 members from across the United States, PUNC has created an online community consisting of its Web site (nanocooperative.org), a weekly online summer group meeting program for faculty and students, and a Discord server for informal conversations. Additionally, in-person symposia at ACS conferences and PUNC-specific conferences are planned for the future. It is our hope that in the years to come PUNC will be seen as a model organization for community building and research support at primarily undergraduate institutions

Protein engineering through chemical, genetic and computational manipulation.

Biocomplexity—the study of complex structures and behaviours that take place in biological systems—goes beyond direct protein production from genes to higher orders of complexity that can be added after a gene has been translated into a protein. These processes can significantly expand the functionality of a protein by adding specific chemical groups to specific sites. The ability to use chemical and enzymatic methods to introduce specific groups into folded proteins is now a powerful strategy to add functional capacity to a protein. This strategy can help to elucidate the role of such post-translational groups on a protein and promises protein therapeutics and glycoconjugate vaccines with optimal properties. Furthermore, a number of methods have been developed towards the total synthesis of proteins. These methods enable the synthesis of complex proteins that have oligosaccharides at pre-defined positions, which cannot be achieved by other means. The sequence of proteins can also be evolved by directed evolution, in order to catalyse the formation of even non-natural bonds, or computationally to design a sequence that has high affinity and specificity for a complementary sequence present on an antigen of interest. This themed issue highlights different approaches by which a protein's structure and functional capacity can be explored, either by adding functional groups or by evolving the native sequence. These approaches may be used to elucidate the role of naturally occurring post-translational modifications, or to create protein conjugates as therapeutics or vaccines. This issue also includes reviews on synthetic antibodies by computational design and the use of proteins as building blocks to create nanostructures