Clustering humans: on biological boundaries

We inquire into the notions of 'boundary' and 'cluster' in the fields of medical genetics, pharmacogenetics, and population genetics. First we show that the two notions are not well discussed in literature. Then we propose a promising explication of them, in which we argue that clustering is always 'property laden', that is, fundamentally dependent on decisions about the properties to be taken into account. In particular we suggest three different kinds of properties (main properties, investigating properties, and catalyzing properties) that have a role in these decisions. That is, we conclude that boundaries and clusters among humans depend on our way of considering nature. Concepts of 'race' and 'ethnic group' are discussed too, since they are the most used clusters among humans.     

Mapping parameter spaces of biological switches

Since the seminal 1961 paper of Monod and Jacob, mathematical models of biomolecular circuits have guided our understanding of cell regulation. Model-based exploration of the functional capabilities of any given circuit requires systematic mapping of multidimensional spaces of model parameters. Despite significant advances in computational dynamical systems approaches, this analysis remains a nontrivial task. Here, we use a nonlinear system of ordinary differential equations to model oocyte selection in Drosophila, a robust symmetry-breaking event that relies on autoregulatory localization of oocyte-specification factors. By applying an algorithmic approach that implements symbolic computation and topological methods, we enumerate all phase portraits of stable steady states in the limit when nonlinear regulatory interactions become discrete switches. Leveraging this initial exact partitioning and further using numerical exploration, we locate parameter regions that are dense in purely asymmetric steady states when the nonlinearities are not infinitely sharp, enabling systematic identification of parameter regions that correspond to robust oocyte selection. This framework can be generalized to map the full parameter spaces in a broad class of models involving biological switches.     

Mapping space by NMR using susceptibility changes at phase boundaries

A technique for differentiating high-resolution NMR signals from different regions of small objects is outlined and some initial results on model systems are given. This method uses inorganic paramagnetic or diamagnetic ions to create magnetic field gradients at phase boundaries.     

Reverse engineering: the architecture of biological networks

We adopt a control theory approach to reverse engineer the complexity of a known system--the bacterial heat shock response. Using a computational dynamic model, we explore the organization of the heat shock system and elucidate its various regulation strategies. We show that these strategies are behind much of the complexity of the network. We propose that complexity is a necessary outcome of robustness and performance requirements that are achieved by the heat shock system's exquisite regulation modules. The techniques we use rely on dynamic computational models and principles from the field of control theory.     

Grand challenges for biological engineering

Biological engineering will play a significant role in solving many of the world's problems in medicine, agriculture, and the environment. Recently the U.S. National Academy of Engineering (NAE) released a document "Grand Challenges in Engineering," covering broad realms of human concern from sustainability, health, vulnerability and the joy of living. Biological engineers, having tools and techniques at the interface between living and non-living entities, will play a prominent role in forging a better future. The 2010 Institute of Biological Engineering (IBE) conference in Cambridge, MA, USA will address, in part, the roles of biological engineering in solving the challenges presented by the NAE. This letter presents a brief outline of how biological engineers are working to solve these large scale and integrated problems of our society.     

Programming and engineering biological networks

Synthetic biology aims to build new functions in living organisms. Recent work has addressed the creation of synthetic epigenetic switches in mammalian cells and synthetic intracellular communication. Fundamentally new, and potentially scaleable, modes of gene regulation have been created that enable expansion of the scope of synthetic circuits. Increasingly sophisticated models of gene regulation that include stochastic effects are beginning to predict the behaviour of small synthetic networks. Overall, these advances suggest that a combination of molecular engineering and systems engineering should allow the creation of living matter capable of performing many useful and novel functions.     

Mapping the lithic colonization at the boundaries of life in Northern Victoria Land,Antarctica

The endolithic microbial communities of the Antarctic represent a borderline lifestyle in the most hostile ice-free areas of the continent. The extreme adaptation of microbes in these communities renders them very sensitive to environmental changes. To date, the actual distribution of these communities has never been investigated; yet, this information would define the geographic limits for life at present and supply a useful tool for monitoring any possible future variation related to climate change. In this study, most of the outcrops of Northern and of one site in Southern Victoria Land were recorded by altitudinal and sea distance gradients. The presence of endolithic life was determined by in situ observation, by microscopic observation of rock fragments in the laboratory, and, for doubtful samples, by culture experiment. Colonizers were present in more than 87 % of the visited sites. The presence of lithic life in Victoria Land appears to be wider than that reported 14 years earlier. The colonization trend follows climatic variation, with epiliths prevailing in coastal sites and decreasing towards the interior, while chasmoendoliths and cryptoendoliths increase and become predominant from the coast towards the inland sites. Typical cryptoendolithic colonization was exclusive on porous rocks as sandstone, chasmoendolithic colonization occurred even in less porous but translucent rocks as granite and quartz. Multivariate analysis of the combined results clearly indicates the pivotal role of the rock type in the colonization of endolithic micro-organisms; sandstone allows lithobionts to push themselves towards areas characterized by harsher conditions.     

Process engineering in biological aerobic waste-water treatment

A non-comprehensive review of several technical developments in the field of aerobic biological waste-water treatment engineering is carried out, considering the active role the engineers have to play in this field. This paper brings together conventional and advanced problems in the field of aerobic biological waste-water treatment. Such an overview of biological waste-water treatment also precedes comments on some important aspects concerning the microorganisms responsible for waste-water treatment as well as considerations of the application of fundamentals and kinetics to the analysis of the biological processes used most commonly for aerobic biological waste-water treatment. A survey of the development of the biological activated-sludge process and some modifications are given. Some problems implied in the conventional activated-sludge waste-water treatment are analyzed, considering conventional processes and bioreactor models (the continuous stirred-tank reactor model and the plug-flow reactor models of the activated-sludge process) as well as aerated lagoons. Further, modifications of the activated-sludge process are presented. These include additional details on the bioreactor progress and applications, with emphasis on aspects concerning airlift bioreactors and their variants, deep-shaft bioreactors and reciprocating jet bioreactors which are considered as the third generation of bioreactors owing to their important advantages in design, operation and performance in waste-water treatment. Sequencing-batch reactors and aerobic digestion processes, including conventional aerobic digestion, high-purity oxygen digestion, thermophilic aerobic digestion and cryophylic aerobic digestion are also reviewed. Finally, some aspects regarding the operational factors that are involved in the selection of the reactor type are included.     

生物工程专业实验教学改革与实践

从生物工程专业实验的课程设置、实验内容、教学方式、考核方式以及为学生提供实验平台等方面进行改革及实践,提升了实验教学质量,提高了学生的整体素质,培养了学生的创新精神,为学生进一步深造或就业奠定了坚实基础。     

Smart thermoresponsive coatings and surfaces for tissue engineering: switching cell-material boundaries

The smart thermoresponsive coatings and surfaces that have been explicitly designed for cell culture are mostly based on poly(N-isopropylacrylamide) (PNIPAAm). This polymer is characterized by a sudden precipitation on heating, switching from a hydrophilic to a hydrophobic state. Mammalian cells cultured on such thermoresponsive substrates can be recovered as confluent cell sheets, while keeping the newly deposited extracellular matrix intact, simply by lowering the temperature and thereby avoiding the use of deleterious proteases. Thermoresponsive materials and surfaces are powerful tools for creating tissue-like constructs that imitate native tissue geometry and mimic its spatial cellular organization. Here we review and compare the most representative methods of producing thermoresponsive substrates for cell sheet engineering.     

Traditional engineering in the biological century: the biotraditional engineer.

The increasing importance of life science in all engineering is prompting departments in the traditional engineering disciplines to offer life science as part of their curricula. Students who take advantage of this opportunity--"biotraditional engineers"--will be well positioned for careers in their discipline and in related areas of bioengineering. The founder engineering societies, such as the Bioengineering Division of ASME, are responding to this trend by broadening their scope and working increasingly across interdisciplinary borders.     

Mapping critical biological motifs and biosynthetic pathways of heparan sulfate

Heparan sulfate (HS) interacts with numerous proteins at the cell surface and orchestrates myriad biological events. Unraveling the mechanisms of these events at the molecular level calls for the structural analysis of these negatively charged and highly heterogeneous biopolymers. However, HS is often available only in small quantities, and the task of structural analysis necessitates the use of ultra-sensitive methods, such as mass spectrometry. Sequence heterogeneity within HS chains required us to identify critical functional groups and their spacing to determine structure-function relationships for HS. We carried out structural analysis of HS isolated from wild type, 3-OST-1, 3-OST-3A, or 3-OST-5 sulfotransferase-transduced Chinese hamster ovary cells and also from various tissues. In the context of tissue-specific HS, the data allowed us to map the biosynthetic pathways responsible for the placement of critical groups. As a means of determining the distance between critical groups within a motif, we determined the spacing of the rare GlcNAc-GlcA disaccharide sequence in the completely desulfated re-N-sulfated porcine intestinal heparin. These disaccharides are biosynthetic regulatory markers for 3-OST-1 modification and the partial structure of the antithrombin III binding site. They occur only at the distance of hexasaccharide, octasaccharide, decasaccharide, or dodecasaccharide. Thus this approach allowed us to map both the biosynthetic pathways for generating critical functional groups and their spacing within HS. Our new strategy removes two obstacles to rapid progress in this field of research.     

Change is necessary in a biological engineering curriculum

Success of a Biological Engineering undergraduate educational program can be measured in a number of ways, but however it is measured, a presently successful program can translate into an unsuccessful program if it cannot adjust to different conditions posed by technical advances, student characteristics, and academic pressures. Described in this paper is a Biological Engineering curriculum that has changed significantly since its transformation from Agricultural Engineering in 1993. As a result, student numbers have continued to climb, specific objectives have emerged, and unique courses have been developed. The Biological Resources Engineering program has evolved into a program that emphasizes breadth, fundamentals, communications skills, diversity, and practical engineering judgment.     

野生型组织型纤溶酶原激活剂(t-PA)工程细胞株生物学特性分析

野生型t-PA工程细胞4B3形态与亲代细胞CHO-dhfr-相似呈多角形,类似上皮细胞。在MTX加压达5×10~(-7)mol/L时,少数细胞略变瘦长,但仍显多角形,形态正常。细胞无血清培养上清经FAPA检测,亚克隆株表达水平为10~6细胞4000～5000IU/24h。细胞经体外传代3个月及冻存3个月后复苏,部分亚克隆株表达水平下降,多数仍为10~6细胞4000IU/24h,表明4B3细胞株稳定性好。裸鼠试验表明,该工程株活细胞、细胞DNA、纯化的4B3rt-PA均无致瘤性病毒,支原体检查为阴性。遗传特性分析表明,该工程细胞与其亲代细胞CHO-dhfr-细胞染色体数均为20条,均有不同程度不同类型的畸变。该工程细胞的畸变率为16％。CHO-dhfr-细胞畸变率为6％。属正常范围。结果表明4B3细胞株为高效表达的性能优良的工程细胞株。     

Mapping the importance of four factors in creating monovalent ion selectivity in biological molecules

The ability of macrocycles, enzymes, ion channels, transporters, and DNA to differentiate among ion types is often crucial to their function. Using molecular dynamics simulations on both detailed systems and simple models, we quantify the importance of several factors which affect the ion selectivity of such molecules, including the number of coordinating ligands, their dipole moment, and their vibrational motion. The information resulting from our model systems is distilled into a series of selectivity maps that can be used to read off the relative free energy associated with binding of different ions, and to provide an estimate of the importance of the various factors. Although our maps cannot capture all elements of real systems, it is remarkable that they produce differential site-binding energies that are in line with experiment and more-detailed simulations for a variety of systems—making them useful for understanding the origins of selective binding and transport. The chemical nature of the coordinating ligands is essential for creating thermodynamic ion selectivity in flexible molecules (such as 18c6), but as the binding site becomes more rigid, the number of ligands (as in ion channels) and the reduction of thermal fluctuations (as in amino-acid transporters) can become important. In the future, our maps could aid in the determination of the local structure from binding energies and assist in the design of novel ion selective molecules.     

Taking the example of computer systems engineering for the analysis of biological cell systems

In this paper, we discuss the potential for the use of engineering methods that were originally developed for the design of embedded computer systems, to analyse biological cell systems. For embedded systems as well as for biological cell systems, design is a feature that defines their identity. The assembly of different components in designs of both systems can vary widely. In contrast to the biology domain, the computer engineering domain has the opportunity to quickly evaluate design options and consequences of its systems by methods for computer aided design and in particular design space exploration. We argue that there are enough concrete similarities between the two systems to assume that the engineering methodology from the computer systems domain, and in particular that related to embedded systems, can be applied to the domain of cellular systems. This will help to understand the myriad of different design options cellular systems have. First we compare computer systems with cellular systems. Then, we discuss exactly what features of engineering methods could aid researchers with the analysis of cellular systems, and what benefits could be gained.     

Taking the example of computer systems engineering for the analysis of biological cell systems

In this paper, we discuss the potential for the use of engineering methods that were originally developed for the design of embedded computer systems, to analyse biological cell systems. For embedded systems as well as for biological cell systems, design is a feature that defines their identity. The assembly of different components in designs of both systems can vary widely. In contrast to the biology domain, the computer engineering domain has the opportunity to quickly evaluate design options and consequences of its systems by methods for computer aided design and in particular design space exploration. We argue that there are enough concrete similarities between the two systems to assume that the engineering methodology from the computer systems domain, and in particular that related to embedded systems, can be applied to the domain of cellular systems. This will help to understand the myriad of different design options cellular systems have. First we compare computer systems with cellular systems. Then, we discuss exactly what features of engineering methods could aid researchers with the analysis of cellular systems, and what benefits could be gained.     

Biochemical engineering of the N-acyl side chain of sialic acid: biological implications

N-Acetylneuraminic acid is the most prominent sialic acid in eukaryotes. The structural diversity of sialic acid is exploited by viruses, bacteria, and toxins and by the sialoglycoproteins and sialoglycolipids involved in cell-cell recognition in their highly specific recognition and binding to cellular receptors. The physiological precursor of all sialic acids is N-acetyl D-mannosamine (ManNAc). By recent findings it could be shown that synthetic N-acyl-modified D-mannosamines can be taken up by cells and efficiently metabolized to the respective N-acyl-modified neuraminic acids in vitro and in vivo. Successfully employed D-mannosamines with modified N-acyl side chains include N-propanoyl- (ManNProp), N-butanoyl- (ManNBut)-, N-pentanoyl- (ManNPent), N-hexanoyl- (ManNHex), N-crotonoyl- (ManNCrot), N-levulinoyl- (ManNLev), N-glycolyl- (ManNGc), and N-azidoacetyl D-mannosamine (ManNAc-azido). All of these compounds are metabolized by the promiscuous sialic acid biosynthetic pathway and are incorporated into cell surface sialoglycoconjugates replacing in a cell type-specific manner 10-85% of normal sialic acids. Application of these compounds to different biological systems has revealed important and unexpected functions of the N-acyl side chain of sialic acids, including its crucial role for the interaction of different viruses with their sialylated host cell receptors. Also, treatment with ManNProp, which contains only one additional methylene group compared to the physiological precursor ManNAc, induced proliferation of astrocytes, microglia, and peripheral T-lymphocytes. Unique, chemically reactive ketone and azido groups can be introduced biosynthetically into cell surface sialoglycans using N-acyl-modified sialic acid precursors, a process offering a variety of applications including the generation of artificial cellular receptors for viral gene delivery. This group of novel sialic acid precursors enabled studies on sialic acid modifications on the surface of living cells and has improved our understanding of carbohydrate receptors in their native environment. The biochemical engineering of the side chain of sialic acid offers new tools to study its biological relevance and to exploit it as a tag for therapeutic and diagnostic applications.