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RESEARCH


         ALSO IN SCIENCE JOURNALS
                                            Edited by Stella Hurtley


        SCIENCE COMMUNITY          that are usually clustered   PROTEIN DESIGN           IMMUNE ENGINEERING
        The whys and               in “defense islands” in their   Membrane protein      Engineering cytokine-
                                   genomes. Doron et al. took
        wherefores of SciSci       advantage of this property to   oligomers by design   receptor pairs
        The science of science (SciSci)   map microbial defense sys-  In recent years, soluble protein   Interleukin-2 (IL-2) is an
        is based on a transdisciplinary   tems systematically (see the   design has achieved successes   important cytokine that helps
        approach that uses large data   Perspective by Kim). Candidate   such as artificial enzymes and   T cells destroy tumors and
        sets to study the mechanisms   immune systems were then   large protein cages. Membrane   virus-infected cells. IL-2 has
        underlying the doing of sci-  experimentally validated for   proteins present a considerable   great therapeutic promise
        ence—from the choice of a   their activities. Like well-known   design challenge, but here too   but is limited by toxic side
        research problem to career   defense arsenals such as restric-  there have been advances,   effects and its capacity to both
        trajectories and progress within   tion-modification and CRISPR   including the design of a zinc-  activate and repress immune
        a field. In a Review, Fortunato et   systems, these additional   transporting tetramer. Lu et   responses. Sockolosky et al.
        al. explain that the underlying   immune systems now require   al. report the design of stable   set out to improve IL-2–based
        rationale is that with a deeper   mechanistic investigation and   transmembrane monomers,   immunotherapy by engineer-
        understanding of the precur-  could potentially be engineered   homodimers, trimers, and   ing synthetic IL-2–receptor
        sors of impactful science, it will   into useful molecular tools in the   tetramers with up to eight mem-  pairs (i.e., IL-2 and its receptor,
        be possible to develop systems   future. —SYM         brane-spanning regions in an   IL-2R) (see the Perspective by
        and policies that improve each     Science, this issue p. 1008;   oligomer. The designed proteins   Mackall). Engineered complexes
        scientist’s ability to succeed            see also p. 993  adopted the target oligomeriza-  transmitted IL-2 signals but only
        and enhance the prospects of                          tion state and localized to the   interacted with each other and
        science as a whole. —BJ                               predicted cellular membranes,   not with endogenous IL-2/IL-2R.
                 Science, this issue p. 1007  OPTICS          and crystal structures of the   Treatment of mice with IL-2
                                   Exploring photonic         designed dimer and tetramer   improved the ability of engi-
                                                              reflected the design models.   neered T cells to reject tumors
                                   topology
        NEUROSCIENCE                                          —VV                        with no obvious side effects. This
        How to select and shape    Scattering topological effects     Science, this issue p. 1042  type of approach may provide a
                                   are being explored in a variety of                    way to mitigate toxicities associ-
        neural activity            electronic and optical materials                      ated with some cytokine-based
        When we learn a new skill   systems owing to their robust-  NEUROIMMUNOLOGY      immunotherapies. —PNK
        or task, our movements are   ness against defects (see the   An off switch for helminth   Science, this issue p. 1037;
        reinforced and shaped. Learning   Perspective by Özdemir). Yang                                 see also p. 990
        occurs because the neural activ-  et al. designed and fabricated   immunity
        ity patterns in the movement   an ideal optical analog of a   Group 2 innate lymphoid cells
        control–related brain regions   three-dimensional Weyl system.   (ILC2s) are involved in responses   ECOLOGY
        that are rewarded are repeated.   Angular transmission measure-  to helminths, viruses, and   Fostering the resilience
        But how does this reinforcement   ments revealed four Weyl points   allergens. Moriyama et al. found
        work? Athalye et al. developed a   at the same energy, as well as   that ILC2s interact with the   of ecosystems
        closed-loop self-stimulation par-  the signature helicoidal arcs   nervous system to modulate   What makes an ecosystem
        adigm in which a target motor   associated with such an exotic   helminth immunity. ILC2s from   resilient to environmental
        cortical activity pattern resulted   topological system. Zhou et   the small intestine expressed the   change? Answering this ques-
        in the optogenetic stimulation   al. theoretically proposed and   b -adrenergic receptor (b AR),   tion is increasingly important
                                                               2                2
        of dopaminergic neurons.   experimentally demonstrated   which normally interacts with   as climate change and other
        With training, mice learned to   the formation of a topologically   the neurotransmitter epineph-  stressors affect ecosystems
        reenter specific neuronal activity   protected bulk Fermi arc. They   rine. Inactivating b AR resulted   around the world. But, as Willis
                                                                           2
        patterns, which triggered self-  attributed the formation of the   in lower helminth burden and   et al. explain in a Perspective,
        stimulation and shaped their   arc to the topological nature of   more ILC2s, eosinophils, and   identifying resilient ecosystems
        neural activity to be closer to the   paired exceptional points (points   type 2 cytokine production in   and determining the factors
        target pattern. —PRS       at which gain and loss in the   mice. Conversely, treatment of   behind their resilience can be
                 Science, this issue p. 1024  system are matched). Photonic   helminth-infected mice with a   difficult. Focusing on tropical
                                   crystals may provide a power-  b AR agonist enhanced worm   ecosystems, the authors outline
                                                               2
                                   ful platform for studying exotic   burden and reduced proliferation   the many biotic and abiotic
        MICROBIOLOGY               properties of topological elec-  of ILC2s. Thus, b AR negatively   factors contributing to resilience
                                                                          2
        Maps of defense arsenals   tronic systems and may also be   regulates ILC2-driven protective   and highlight recent studies
                                   used to develop optical devices   immunity. —PNK      that provide pointers for future
        in microbial genomes       that exploit topological proper-   Science, this issue p. 1056  research and conservation
        To survive the attack of foreign   ties of light-matter interactions.            aimed at fostering resilience.
        invaders such as viruses and   —ISO                                              In another Perspective, Darling
        plasmids, bacteria and archaea   Science, this issue p. 1013, p. 1009;           and Côté discuss whether
        fight back with immune systems            see also p. 995                        coral reef ecosystems might be

        1006-B    2 MARCH 2018 • VOL 359 ISSUE 6379                                            sciencemag.org  SCIENCE
                                                       Published by AAAS

   DA_0302ISIO.indd   1007                                                                                   2/28/18   10:51 AM
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