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Over the past decade, modern optogenetics has emerged from the convergence of developments in microbial opsin engineering, genetic methods for targeting, and optical strategies for light delivery. In this Historical Commentary, Karl Deisseroth reflects on the optogenetic landscape, from the important steps but slow progress in the beginning to the acceleration in discovery seen in recent years. Over the past 10 years, the development and convergence of microbial opsin engineering, modular genetic methods for cell-type targeting and optical strategies for guiding light through tissue have enabled versatile optical control of defined cells in living systems, defining modern optogenetics. Despite widespread recognition of the importance of spatiotemporally precise causal control over cellular signaling, for nearly the first half (2005–2009) of this 10-year period, as optogenetics was being created, there were difficulties in implementation, few publications and limited biological findings. In contrast, the ensuing years have witnessed a substantial acceleration in the application domain, with the publication of thousands of discoveries and insights into the function of nervous systems and beyond. This Historical Commentary reflects on the scientific landscape of this decade-long transition.

For the past 25 years NIH Image and ImageJ software have been pioneers as open tools for the analysis of scientific images. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.

Single-particle cryo-electron microscopy (cryo-EM) has emerged over the last two decades as a technique capable of studying the structure of challenging systems. The author of this Commentary discusses some of the major historical landmarks in cryo-EM that have led to its present success. Single-particle cryo-electron microscopy (cryo-EM) has emerged over the last two decades as a technique capable of studying challenging systems that otherwise defy structural characterization. Recent technical advances have resulted in a 'quantum leap' in applicability, throughput and achievable resolution that has gained this technique worldwide attention. Here I discuss some of the major historical landmarks in the development of the cryo-EM field, ultimately leading to its present success.

Immunology offers an unprecedented opportunity for the science-driven development of therapeutics. The successes of antibodies to the immunomodulatory receptor CTLA-4 and blockade of the immunoinhibitory receptor PD-1 in cancer immunotherapy, from gene discovery to patient benefit, have created a paradigm for driving such endeavors.

One hundred years ago the birth of immunology was made official by the Nobel Prize award to Elie Metchnikoff and Paul Ehrlich. Metchnikoff discovered phagocytosis by macrophages and microphages as a critical host-defense mechanism and thus is considered the father of cellular innate immunity. Ehrlich described the side-chain theory of antibody formation and the mechanisms of how antibodies neutralize toxins and induce bacterial lysis with the help of complement and thus is considered one of the fathers of humoral adaptive immunity. Despite many discordant discussions in the initial phase after these discoveries, innate and adaptive responses are now known to be complementary partners in producing robust immunity.

The idea of using hybrid proteins containing transcription factor domains to analyze protein-protein interactions was described in 1989. Over the past 25 years, this method has begun to reveal the complex protein networks that underlie cellular behavior.

Long before mass spectrometry became an important tool for cell biology, it was yielding scientific insights in physics and chemistry. Here is a brief history of how the technology has expanded from a tool for studying atomic structure and characterizing small molecules to its current incarnation as the most powerful technique for analyzing proteomes.

Twenty-five years after its identification, the transcription factor NF-κB continues to attract intense effort from a large and diverse research community. Ranjan Sen offers a personal account of the discovery of NF-κB.

From histology to microcinematography, from cytochemistry to live cell imaging, the history of visualization technology in the life sciences may be understood as a series of cycles of action and reaction between static and dynamic modes of representing life.

October 2007 marks the 50th anniversary of the publication of Frank Macfarlane Burnet's clonal selection theory in the Australian Journal of Science . This short article, republished at the end of this commentary, revolutionized the field of immunology.