Towards synthetic cells:are cells computers making computers?

Understanding life supposes that one will,one day,reconstruct cells. A deep analysis of what life is shows that a cell is similar to a computers making computer. This asks for several orginal levels of organisation. First,the cell needs to be seen as a machine separated from the genetic program,which it runs. Over generations the machine reproduces,while the program replicates. Reproduction is a process which is able to accumulate valuable information over generations. Extracting valuable information from an ocean of noise requires an energy-dependent process which uses energy to prevent degradation of functional entities. Analysis of bacterial genomes shows that the core set of genes which persist in most genomes code for the functions needed to perform this process of ratchet-like information accumulation. It also suggests that a mineral,polyphosphates,could be a ubiquitous (and stable) energy source essential for the process.     

Information of the chassis and information of the program in synthetic cells

Synthetic biology aims at reconstructing life to put to the test the limits of our understanding. It is based on premises similar to those which permitted invention of computers, where a machine, which reproduces over time, runs a program, which replicates. The underlying heuristics explored here is that an authentic category of reality, information, must be coupled with the standard categories, matter, energy, space and time to account for what life is. The use of this still elusive category permits us to interact with reality via construction of self-consistent models producing predictions which can be instantiated into experiments. While the present theory of information has much to say about the program, with the creative properties of recursivity at its heart, we almost entirely lack a theory of the information supporting the machine. We suggest that the program of life codes for processes meant to trap information which comes from the context provided by the environment of the machine.     

Synthetic biology of minimal living cells: primitive cell models and semi-synthetic cells

This article summarizes a contribution presented at the ESF 2009 Synthetic Biology focused on the concept of the minimal requirement for life and on the issue of constructive (synthetic) approaches in biological research. The attempts to define minimal life within the framework of autopoietic theory are firstly described, and a short report on the development of autopoietic chemical systems based on fatty acid vesicles, which are relevant as primitive cell models is given. These studies can be used as a starting point for the construction of more complex systems, firstly being inspired by possible origins of life scenarioes (and therefore by considering primitive functions), then by considering an approach based on modern biomacromolecular-encoded functions. At this aim, semi-synthetic minimal cells are defined as those man-made vesicle-based systems that are composed of the minimal number of genes, proteins, biomolecules and which can be defined as living. Recent achievements on minimal sized semi-synthetic cells are then discussed, and the kind of information obtained is recognized as being distinctively derived by a constructive approach. Synthetic biology is therefore a fundamental tool for gaining basic knowledge about biosystems, and it should not be confined at all to the engineering side.     

The Cell Biology of the Endocytic System from an Evolutionary Perspective

Evolutionary cell biology can afford an interdisciplinary comparative view that gives insights into both the functioning of modern cells and the origins of cellular systems, including the endocytic organelles. Here, we explore several recent evolutionary cell biology studies, highlighting investigations into the origin and diversity of endocytic systems in eukaryotes. Beginning with a brief overview of the eukaryote tree of life, we show how understanding the endocytic machinery in a select, but diverse, array of organisms provides insights into endocytic system origins and predicts the likely configuration in the last eukaryotic common ancestor (LECA). Next, we consider three examples in which a comparative approach yielded insight into the function of modern cellular systems. First, using ESCRT-0 as an example, we show how comparative cell biology can discover both lineage-specific novelties (ESCRT-0) as well as previously ignored ancient proteins (Tom1), likely of both evolutionary and functional importance. Second, we highlight the power of comparative cell biology for discovery of previously ignored but potentially ancient complexes (AP5). Finally, using examples from ciliates and trypanosomes, we show that not all organisms possess canonical endocytic pathways, but instead likely evolved lineage-specific mechanisms. Drawing from these case studies, we conclude that a comparative approach is a powerful strategy for advancing knowledge about the general mechanisms and functions of endocytic systems.The endomembrane system mediates transport of lipids, proteins, and other molecules to the various locations in the eukaryotic cell. It also underlies the interactions with the extracellular environment, presenting material at the cell surface as well as secreting and internalizing material. In modern cells, these latter aspects are important for signal transduction, surface remodeling, and nutrient acquisition. Just as these abilities are crucial to modern cells, they were likely equally important for the very first eukaryotes as they underwent speciation from prokaryotic-like ancestors via niche competition in the ancient world (Cavalier-Smith 2002). Understanding the events and biological processes involved in the evolution of the membrane-trafficking system in general, and the endocytic system in particular, gives us insights into landmark events in our cellular past.Evolutionary insight about cellular phenomenon is derived from two basic types of comparative study: from molecular cell biological analyses of increasingly tractable model organisms across the diversity of eukaryotes, and by computational analyses of genomic information (i.e., the genes encoding the membrane-trafficking machinery). Whereas the information gathered from taking this comparative, or evolutionary cell biology, approach (Brodsky et al. 2012) is valuable for evolutionary content, these same analyses are potentially highly valuable in understanding basic cell biology, a benefit that is perhaps less obvious and hence less appreciated. In this article, we frame what has been learned about the evolution of the endocytic system, in the dual context of what it tells us about ancient cells together with what it can tell us about modern ones. We begin with a brief introduction to eukaryotic diversity and the evolution of the membrane-trafficking system. We then delve into the evolution of specific endocytic factors to illustrate the ways in which cell biologists of all stripes can benefit from the emerging field of evolutionary cell biology.     

Predicted elements of telomere organization and function in Ustilago maydis

Telomeres are specialized caps of nucleoprotein complexes located at the chromosome termini. They consist of short DNA repeats and of an assortment of associated proteins whose function is currently under intense investigation in model systems. These specialized structures protect the linear ends of eukaryotic chromosomes against DNA repair and degradation activities, and serve as the substrate for telomerase, the ribonucleoprotein complex that synthesises the telomere repeats. The pivotal role of the telomeres in the maintenance of cell viability in several model eukaryotes, including humans, greatly promoted research in telomere biology. Studies on telomere structure and function in fungi other than model systems are limited to providing information on the telomeric repeat sequences. Here, we have summarized the current knowledge on the organization of chromosome ends and on the proteins participating in telomere function in model systems including recent information obtained for filamentous fungi. We also describe Ustilago maydis genes that are potential homologs of proteins known from other systems to participate in telomere biology.     

A nonlinear regression program for small computers

A BASIC computer program for performing weighted nonlinear regression is described and a listing of the program is given. The program, which is small and simple to use, has been designed to be run by users with little knowledge of mathematics or computers. Robust methods of analysis are described which may be applied to data in which experimental errors are not normally distributed, and the program incorporates one such method. It is shown that the program is useful for the analysis of data conforming to the Michaelis-Menten equation, a single exponential, and to binding equations, and other applications are discussed.     

Transfer of genetic information in an organism

New knowledge in biology led us to a better understanding of organization and functioning of living organisms. Today, re-evaluation of our concept of human biology is taking place. Theoretical analysis shows that taking into account the complexity of the organism and frequency of spontaneous mutations, it is impossible to explain the real time of organismal life. Therefore, besides extant systems, other repair systems must also exist. There are three "levels" at which a cell population withstands mutational pressure. First - intracellular (repair), second - intercellular (all forms of informational flows), and third - cellular replacement. Stem cells undertake regenerative functions following damage at the level of the tissue. They are also influenced by mutations, and for stem cells, it is most important that they preserve and support their full activity.     

Human embryonic stem cells: emerging technologies and practical applications

Human embryonic stem cells possess the unique ability to differentiate into any adult cell type. Recent advances in the understanding of stem cell biology make new applications possible for stem cell based technology. Of note, it is now possible to reprogram terminally differentiated human somatic cells into pluripotent cells that are functionally equivalent to embryonic stem cells. These induced pluripotent cells may become the substrate for future disease models and cell-based therapies. In addition, novel techniques for genetic manipulation have increased the ease with which genes can be modified into stem cells. In this review, we describe these novel technologies as well as developments in the understanding of basic biology of stem cell pluripotency and differentiation.     

Functional proteomics to exploit genome sequences.

The sequencing of various genomes has inaugurated a new stage in the understanding of normal and pathological cell function through the analysis of the role of proteins. Proteins, after all, that intervene in the different molecular mechanisms of life, during growth, reproduction, and in the interaction between cells, thus making it possible to describe the biology of integrated systems. In this article, we briefly describe the various stages in the progression of our knowledge, from the genome to the "functional" proteome. Emphasis is placed on a global approach to the protein-protein interactions used to describe the cellular "interactome".     

At the dawn of a new revolution in life sciences

In a recently published article Sydney Brenner argued that the most relevant scientific revolution in biology at his time was the breakthrough of the role of "information" in biology.The fundamental concept that integrates this new biological "information" with matter and energy is the universal Turing machine and von Neumann's self-reproducing machines.In this article we demonstrate that in contrast to Turing/von Neumann machines living cells can really reproduce themselves.Additionally current knowledge on the roles of noncoding RNAs indicates a radical violation of the central dogma of molecular biology and opens the way to a new revolution in life sciences.     

Comparing plant and animal extracellular matrix-cytoskeleton connections — are they alike?

Summary Cell adhesion and communication is one of the most fascinating fields of modern biology. How do cells receive information from the environment and from neighboring cells? How does this information elicit morphogenesis, cell division and migration? The recent identification of the surface molecules involved in these events in animal systems is beginning to disclose that a continuum, extracellular matrix-plasma membrane-cytoskeleton, may be a common structure present in all eukaryotic cells. In this article we compare current knowledge on this complex structure in animal systems to the emerging data on plants. We point out the areas that need additional research to fully understand the role of the cell wall-cytoskeleton continuum in plants.Abbreviations ABP actin-binding protein - AGP arabinogalactan proteins - CTK cytoskeleton - ECM extracellular matrix - FN fibronectin - hFN human fibronectin - HRGP hydroxyproline-rich glycoproteins - hVN human vitronectin - PM plasma membrane - SAM substrate adhesion molecule - VN vitronectin Dedicated to Professor Dr. Hartmut K. Lichtenthaler on the occasion of his 60th birthday     

Autophagy in stem cells

Autophagy is a highly conserved cellular process by which cytoplasmic components are sequestered in autophagosomes and delivered to lysosomes for degradation. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining cellular homeostasis as well as remodeling during normal development, and dysfunctions in autophagy have been associated with a variety of pathologies including cancer, inflammatory bowel disease and neurodegenerative disease. Stem cells are unique in their ability to self-renew and differentiate into various cells in the body, which are important in development, tissue renewal and a range of disease processes. Therefore, it is predicted that autophagy would be crucial for the quality control mechanisms and maintenance of cellular homeostasis in various stem cells given their relatively long life in the organisms. In contrast to the extensive body of knowledge available for somatic cells, the role of autophagy in the maintenance and function of stem cells is only beginning to be revealed as a result of recent studies. Here we provide a comprehensive review of the current understanding of the mechanisms and regulation of autophagy in embryonic stem cells, several tissue stem cells (particularly hematopoietic stem cells), as well as a number of cancer stem cells. We discuss how recent studies of different knockout mice models have defined the roles of various autophagy genes and related pathways in the regulation of the maintenance, expansion and differentiation of various stem cells. We also highlight the many unanswered questions that will help to drive further research at the intersection of autophagy and stem cell biology in the near future.     

Evolutionarily conserved concepts in glial cell biology

The evolutionary conservation of glial cells has been appreciated since Ramon y Cajal and Del Rio Hortega first described the morphological features of cells in the nervous system. We now appreciate that glial cells have essential roles throughout life in most nervous systems. The field of glial cell biology has grown exponentially in the last ten years. This new wealth of knowledge has been aided by seminal findings in non-mammalian model systems. Ultimately, such concepts help us to understand glia in mammalian nervous systems. Rather than summarizing the field of glial biology, I will first briefly introduce glia in non-mammalian models systems. Then, highlight seminal findings across the glial field that utilized non-mammalian model systems to advance our understanding of the mammalian nervous system. Finally, I will call attention to some recent findings that introduce new questions about glial cell biology that will be investigated for years to come.     

Immortalized cells as experimental models to study cancer

The development of cancer is a multi-step process in which normal cells sustain a series of genetic alterations that together program the malignant phenotype. Much of our knowledge of cancer biology results from the detailed study of specimens and cell lines derived from patient tumors. While these approaches continue to yield critical information regarding the identity, number, and types of alterations found in human tumors, further progress in understanding the molecular basis of malignant transformation depends upon the generation and use of increasingly sophisticated experimental models of cancer. Over the past several years, the recognition that telomeres and telomerase play essential roles in regulating cell lifespan now permits the development of new models of human cancer. Here we review recent progress in the use of immortalized human cells as a foundation for understanding the molecular basis of cancer.     

动物细胞培养过程中的细胞凋亡

细胞培养过程中的细胞凋亡是细胞受环境因素的影响而发生的现象。随着对细胞凋亡的分子生物学和细胞生物学了解的深入,显示了有效地控制动物细胞培养中细胞凋亡的巨大潜力。包括采用ＤＮＡ重组技术把抗细胞凋亡的基因导入细胞和在培基中加入具有抗细胞凋亡的生存因子或化合物等手段已用于控制细胞培养过程中的细胞凋亡。这些技术将大大延长细胞达到饱和密度后的培养时间,提高细胞培养系统的生产效率。