Bridging the gap between physics and biology.

The work is devoted to the historical development of physics and biology. Various aspects of their interactions are shown: antagonism, mutual penetration and a lot of bridges, built or being built between them. The gradual "evolution of the world picture" from going away of the "pre-scientific" animated Universe and the appearance of mechanicism and vitalism to the development of systems and field approaches is traced. The last part of the paper is concerned with some present-day works at the joint between physics and biology.     

Bridging the gap

Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base.     

Molecular imaging: Bridging the gap between neuroradiology and neurohistology

Historically, in vivo imaging methods have largely relied on imaging gross anatomy. More recently it has become possible to depict biological processes at the cellular and molecular level. These new research methods use magnetic resonance imaging (MRI), positron emission tomography (PET), near-infrared optical imaging, scintigraphy, and autoradiography in vivo and in vitro. Of primary interest is the development of methods using MRI and PET with which the progress of gene therapy in glioblastoma (herpes simplex virus-thymidine kinase) and Parkinson's disease can be monitored and graphically displayed. The distribution of serotonin receptors in the human brain and the duration of serotonin-receptor antagonist binding can be assessed by PET. With PET, it is possible to localize neurofibrillary tangles (NFTs) and beta-amyloid senile plaques (APs) in the brains of living Alzheimer disease (AD) patients. MR tracking of transplanted oligodendrocyte progenitors is feasible for determining the extent of remyelinization in myelin-deficient rats. Stroke therapy in adult rats with subventricular zone cells can be monitored by MRI. Transgene expression (beta-galactosidase, tyrosinase, engineered transferrin receptor) can also be visualized using MRI. Macrophages can be marked with certain iron-containing contrast agents which, through accumulation at the margins of glioblastomas, ameliorate the visual demarcation in MRI. The use of near-infrared optical imaging techniques to visualize matrix-metalloproteinases and cathepsin B can improve the assessment of tumor aggressiveness and angiogenesis-inhibitory therapy. Apoptosis could be detected using near-infrared optical imaging representation of caspase 3 activity and annexin B. This review demonstrates the need for neurohistological research if further progress is to be made in the emerging but burgeoning field of molecular imaging.     

Bridging the gap between theory and data in ecological models

In September 2011, the University of Essex, UK, hosted an interdisciplinary conference, Mathematical and Theoretical Ecology 2011 (MATE 2011), with the theme of ‘Linking models with ecological processes’. The aim of the meeting was to create discussion and debate between modellers and empiricists working in ecology. A wide range of topics were discussed at the meeting including evolutionary and community models of ecosystem structure, epidemiological models, non-linear models of population dynamics, spatiotemporal models, individual and collective movement behaviour, and applications of ecological models to engineering problems. In this introductory article, we provide a report of the MATE 2011 meeting, and briefly review the most recent relevant research in the fields of mathematical and theoretical ecology. We introduce and summarise the eight contributed articles that were selected for this special issue. The diverse range of topics and the wide range of mathematical, statistical and computational tools used illustrate the broad appeal and depth of research in the rich field of mathematical and theoretical ecology.     

Bridging the gap between research and applications in the Third World

In most developing countries a gap separates the research establishment from the applied sector. As a consequence, results from indigenous research are not transferred to those who may be able to apply them in industry, health and agriculture, i.e. to the technology end-user. Two factors create and sustain the gap: (1) mechanisms that promote and facilitate technology transfer from laboratories to industry or farmers either do not exist or are poorly developed in these countries; and (2) obsolete but tenacious economic, legal, and social barriers exist that prevent university-industry co-operation. It is reasonable to assume that developing countries will be unable to benefit fully from biotechnology, in terms of economic development and problem solving, unless they are able to utilize results from indigenous biotechnological research. Bridging the gap between research and applications is therefore of vital importance. Accordingly, the aim of this paper is to consider what governments and international agencies can do to bridge this gap and to demarcate specific measures that they can implement relatively quickly and easily. The focus throughout this paper is on capability building in biotechnology, especially as it affects researchers and technology end-users in the Third World. This depends to a great extent on setting up technology-transfer units in universities and industries, staffed by professionals whose raison d'être would be to make certain that research results are indeed applied.This paper was presented at the UNIDO Expert Group Meeting on Applications of Biotechnology to Food Processing in Africa, held in Ibadan, Nigeria, in December 1991.     

Bridging the gap between structure and kinetics of human SGLT1

The Na(+)-glucose cotransporter hSGLT1 is a member of a class of membrane proteins that harness Na(+) electrochemical gradients to drive uphill solute transport. Although hSGLT1 belongs to one gene family (SLC5), recent structural studies of bacterial Na(+) cotransporters have shown that Na(+) transporters in different gene families have the same structural fold. We have constructed homology models of hSGLT1 in two conformations, the inward-facing occluded (based on vSGLT) and the outward open conformations (based on Mhp1), mutated in turn each of the conserved gates and ligand binding residues, expressed the SGLT1 mutants in Xenopus oocytes, and determined the functional consequences using biophysical and biochemical assays. The results establish that mutating the ligand binding residues produces profound changes in the ligand affinity (the half-saturation concentration, K(0.5)); e.g., mutating sugar binding residues increases the glucose K(0.5) by up to three orders of magnitude. Mutation of the external gate residues increases the Na(+) to sugar transport stoichiometry, demonstrating that these residues are critical for efficient cotransport. The changes in phlorizin inhibition constant (K(i)) are proportional to the changes in sugar K(0.5), except in the case of F101C, where phlorizin K(i) increases by orders of magnitude without a change in glucose K(0.5). We conclude that glucose and phlorizin occupy the same binding site and that F101 is involved in binding to the phloretin group of the inhibitor. Substituted-cysteine accessibility methods show that the cysteine residues at the position of the gates and sugar binding site are largely accessible only to external hydrophilic methanethiosulfonate reagents in the presence of external Na(+), demonstrating that the external sugar (and phlorizin) binding vestibule is opened by the presence of external Na(+) and closes after the binding of sugar and phlorizin. Overall, the present results provide a bridge between kinetics and structural studies of cotransporters.     

Bridging the gap between developmental systems theory and evolutionary developmental biology

Many scientists and philosophers of science are troubled by the relative isolation of developmental from evolutionary biology. Reconciling the science of development with the science of heredity preoccupied a minority of biologists for much of the twentieth century, but these efforts were not corporately successful. Mainly in the past fifteen years, however, these previously dispersed integrating programmes have been themselves synthesized and so reinvigorated. Two of these more recent synthesizing endeavours are evolutionary developmental biology (EDB, or "evo-devo") and developmental systems theory (DST). While the former is a bourgeoning and scientifically well-respected biological discipline, the same cannot be said of DST, which is virtually unknown among biologists. In this review, we provide overviews of DST and EDB, summarize their key tenets, examine how they relate to one another and to the study of epigenetics, and survey the impact that DST and EDB have had (and in future should have) on biological theory and practice.     

Bridging the gap between in vitro and in vivo toxicology testing

In vitro systems for neurotoxicological studies can be useful for the investigation of events associated with pertubations of cellular and molecular targets that are similar to those in the intact animal. The toxicities of organophosphorus compounds, which inhibit esterases, and 1,2,3,6-tetrahydropyridine (MPTP), which depletes dopamine, can be studied in human neuroblastoma cells.