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The subcellular position of a protein is a key determinant of its function. Mounting evidence indicates that RNA localization, where specific mRNAs are transported subcellularly and subsequently translated in response to localized signals, is an evolutionarily conserved mechanism to control protein localization. On-site synthesis confers novel signaling properties to a protein and helps to maintain...
That each of us is truly biologically unique, extending to even monozygotic, “identical” twins, is not fully appreciated. Now that it is possible to perform a comprehensive “omic” assessment of an individual, including one’s DNA and RNA sequence and at least some characterization of one’s proteome, metabolome, microbiome, autoantibodies, and epigenome, it has become abundantly clear that each of us...
Mechanical manipulations of single biological molecules have revealed highly dynamic and mechanical processes at the molecular level. Recent developments have permitted examination of the impact of torque on these processes and visualization of detailed molecular motions, enabling studies of increasingly complex systems. Here we highlight some recent important discoveries.
Synthetic biology seeks to extend approaches from engineering and computation to redesign of biology, with goals such as generating new chemicals, improving human health, and addressing environmental issues. Early on, several guiding principles of synthetic biology were articulated, including design according to specification, separation of design from fabrication, use of standardized biological parts...
The microbiota plays a fundamental role on the induction, training, and function of the host immune system. In return, the immune system has largely evolved as a means to maintain the symbiotic relationship of the host with these highly diverse and evolving microbes. When operating optimally, this immune system-microbiota alliance allows the induction of protective responses to pathogens and the maintenance...
Noncoding RNAs (ncRNAs) accomplish a remarkable variety of biological functions. They regulate gene expression at the levels of transcription, RNA processing, and translation. They protect genomes from foreign nucleic acids. They can guide DNA synthesis or genome rearrangement. For ribozymes and riboswitches, the RNA structure itself provides the biological function, but most ncRNAs operate as RNA-protein...
Cell differentiation is an essential process for the development, growth, reproduction, and longevity of all multicellular organisms, and its regulation has been the focus of intense investigation for the past four decades. The study of natural and induced stem cells has ushered an age of re-examination of what it means to be a stem or a differentiated cell. Past and recent discoveries in plants and...
The health of metazoan organisms requires an effective response to organellar and cellular damage either by repair of such damage and/or by elimination of the damaged parts of the cells or the damaged cell in its entirety. Here, we consider the progress that has been made in the last few decades in determining the fates of damaged organelles and damaged cells through discrete, but genetically overlapping,...
Research into when and where modern humans originated and how they differ from, and interacted with, other now-extinct forms of human has so far been the realm of archaeologists and paleoanthropologists. However, over the past decade, molecular geneticists have begun to study genomes of extinct humans. Here, I discuss where we stand today with respect to understanding how modern humans came to differ...
Once upon a time, immunology was a black box, inflammatory and autoimmune diseases were a mystery, and relatively blunt tools were used to treat these diseases. In the last 40 years, advances in molecular biology, DNA recombination technology, and genome sequencing allowed immunologists to open the box. As the complexity and diversity of the immune response are unveiled, targeted cellular and molecular...
Learning and memory are two of the most magical capabilities of our mind. Learning is the biological process of acquiring new knowledge about the world, and memory is the process of retaining and reconstructing that knowledge over time. Most of our knowledge of the world and most of our skills are not innate but learned. Thus, we are who we are in large part because of what we have learned and what...
Proteins are notorious for their unpleasant behavior—continually at risk of misfolding, collecting damage, aggregating, and causing toxicity and disease. To counter these challenges, cells have evolved elaborate chaperone and quality control networks that can resolve damage at the level of the protein, organelle, cell, or tissue. On the smallest scale, the integrity of individual proteins is monitored...
Isolation of genes encoding the receptors for steroids, retinoids, vitamin D, and thyroid hormone and their structural and functional analysis revealed an evolutionarily conserved template for nuclear hormone receptors. This discovery sparked identification of numerous genes encoding related proteins, termed orphan receptors. Characterization of these orphan receptors and, in particular, of the retinoid...
Comparative genome analyses reveal that organismal complexity scales not with gene number but with gene regulation. Recent efforts indicate that the human genome likely contains hundreds of thousands of enhancers, with a typical gene embedded in a milieu of tens of enhancers. Proliferation of cis-regulatory DNAs is accompanied by increased complexity and functional diversification of transcriptional...
No metazoan cell survives on its own, absent the signals and support of its milieu. For multicellular life with specialized tissues to persist, organization is everything and so defining the association of position with cell state is critical to understanding how tissues function, maintain, and repair. This review focuses specifically on place for progenitor and stem cells. Especially emphasized are...
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