Welcome to our first issue...

Abstract

A quick glance at the scientific advances reported in 2015 will suffice to lead most people to the conclusion that the study of cell function is among the most relevant areas of scientific endeavor today. Since Schleiden and Schwann proposed the cell theory in 1838, biology has changed dramatically and continues to develop at breathtaking speed. The recent advances in gene editing technologies and our understanding of cellular pluripotency suggest that research in cell biology will provide major biomedical breakthroughs in the near future. Inside the Cell was born as a joint effort between scientists and editorial teams to present these advances in an Open Access Forum. This will be possible thanks to the support of a dedicated editorial board with broad experience in different areas of cell research: from microorganisms to human cells and from biochemistry and cell culture to mathematics. Given the expansion of technologies used to study cell function, an important aim of the journal is to provide an integrative view of cellular organization and function. This will be achieved through a combination of primary research papers covering all areas of cell biological research with reviews and commentaries to discuss recent advances in a cellular context. The consequences of such studies for our understanding of human disease or the development of new therapeutic strategies is another area that we wish to represent, hence exemplifying the relevance of cell and molecular biology in today's society. The first issue of Inside the Cell combines reviews discussing some of these recent advances and primary research on a variety of hot topics. In our first published article, Katherine Belov and collaborators discuss the amazing evolutionary immunobiology of transmissible cancers, a topic that by chance became even hotter during the manuscript's revision, with the identification of contagious clam leukemia. Although this area has not received much attention until recently, it will undoubtedly generate new ideas and concepts in cancer evolution and the competition between cancer cells and their environment. Hugh E. Montgomery and colleagues report a new connection between mitochondrial function and cellular metabolism, mediated by the uncoupling proteins. The link – originally identified in genetic studies in two different European populations and then validated in cellular and molecular studies – could explain why drugs for treating hypertension via antagonism of the renin–angiotensin systems also reduce risk of diabetes and metabolic syndrome. Carla V. Finkielstein and Daniel G.S. Capelluto describe the multiple functions of a scaffold protein, Disabled-2, involved in many different pathways in the cell. This protein functions in modulating cell–cell interactions as well as in endocytic pathways, and as a consequence, its deregulation results in a wide spectrum of physiological abnormalities in different cell types. The last few years have witnessed major advances in the therapeutic use of cell cycle inhibitors for cancer therapy. In 2013, polo-like kinase inhibitors received the Food and Drug Administration Breakthrough Therapy designation for treatment of leukemia, and it is hoped that they may join the pipeline of available compounds approved to treat a variety of cancers soon. In this first issue of Inside the Cell, Guillermo de Cárcer and colleagues report the effects of eliminating the polo-like kinase I-encoding gene from the mouse embryo or cultured cells. These data confirm the relevance of this mitotic kinase during development and may set the stage for understanding the possible secondary effects of targeting essential regulatory proteins of this kind in the clinic. The regulation of mitosis is further discussed by the team led by Andrew Burgess in their paper on phosphorylation during mitotic exit. Mitosis is probably the cellular process with the highest level of protein phosphorylation in the cell. Although the role of protein kinases in cell signaling has been analyzed in depth over the last decade, scientists have recently been attracted to studying the relevance and regulation of phosphatases. Burgess et al. discuss recent data on one of the most difficult topics in phosphatase function – how to regulate their specificity – using mitosis as an interesting scenario in which space and time make a major difference to the regulation of these posttranslational modifications. The current issue of Inside the Cell also includes an article by Tanja Dominko and colleagues on replicative life span and the physiological relevance of senescence. The concept of cellular senescence was introduced 50 years ago to refer to intrinsic factors limiting the proliferative life span of cells and studied mainly in vitro. It is now clear that senescence – far from being just a passive byproduct of the replicative limit – is a functionally important contributory factor in development and disease. The complexity of the intrinsic factors influencing senescence is well presented by Dominko et al., providing an appealing framework for future studies in the field in the years to come. In addition to these topics, the past decade will probably be remembered for the extraordinary advances in the genomic manipulation of cells, specifically pluripotent ones. The new techniques that have permitted such progress are very powerful, but they are partly limited by potential off-target effects on the genome. To complete this first issue of Inside the Cell, Stefano Stella and Guillermo Montoya discuss the state of the art by comparing the efficiency of several available tools such as transcription activator-like effectors (TALE) and gene editing techniques based on clustered regularly interspaced short palindromic repeats. This is a very timely topic given that TALE-modified lymphocytes have recently been used to cure a childhood leukemia that was resistant to all other available treatments. Inside the Cell sets out to learn from her more experienced sister journal BioEssays. In addition to primary reports, the evaluation and re-analysis of current data require the generation and discussion of hypotheses that may drive new research efforts. BioEssays has been a point of reference for this kind of scientific publication, and we hope that Inside the Cell and BioEssays will form a synergistic combination that significantly widens and promotes the forum for discussion of scientific advances that are of interest to researchers and the rest of society alike. We wish you interesting reading! Marcos Malumbres Editor-in-Chief Andrew Moore Editor-in-Chief