Immunoscintigraphy for therapy decision making and follow-up of biological therapies

With the availability of new biological therapies there is the need of more accurate diagnostic tools to noninvasively assess the presence of their targets. In this scenario nuclear medicine offers many radiopharmaceuticals for SPECT or PET imaging of many pathological conditions. The availability of monoclonal antibodies provides tools to target specific antigens involved in angiogenesis, cell cycle or modulation of the immune systems. The radiolabelling of such therapeutic mAbs is a promising method to evaluate the antigenic status of each cancer lesion or inflamed sites before starting the therapy. It may also allow to perform follow-up of such biological therapies. In the present review we provide an overview of the most studied radiolabelled antibodies for therapy decision making and follow-up of patients affected by cancer and other pathological conditions

Formulating genome-scale kinetic models in the post-genome era.

The biological community is now awash in high-throughput data sets and is grappling with the challenge of integrating disparate data sets. Such integration has taken the form of statistical analysis of large data sets, or through the bottom-up reconstruction of reaction networks. While progress has been made with statistical and structural methods, large-scale systems have remained refractory to dynamic model building by traditional approaches. The availability of annotated genomes enabled the reconstruction of genome-scale networks, and now the availability of high-throughput metabolomic and fluxomic data along with thermodynamic information opens the possibility to build genome-scale kinetic models. We describe here a framework for building and analyzing such models. The mathematical analysis challenges are reflected in four foundational properties, (i) the decomposition of the Jacobian matrix into chemical, kinetic and thermodynamic information, (ii) the structural similarity between the stoichiometric matrix and the transpose of the gradient matrix, (iii) the duality transformations enabling either fluxes or concentrations to serve as the independent variables and (iv) the timescale hierarchy in biological networks. Recognition and appreciation of these properties highlight notable and challenging new in silico analysis issues

Data-driven modelling of biological multi-scale processes

Biological processes involve a variety of spatial and temporal scales. A holistic understanding of many biological processes therefore requires multi-scale models which capture the relevant properties on all these scales. In this manuscript we review mathematical modelling approaches used to describe the individual spatial scales and how they are integrated into holistic models. We discuss the relation between spatial and temporal scales and the implication of that on multi-scale modelling. Based upon this overview over state-of-the-art modelling approaches, we formulate key challenges in mathematical and computational modelling of biological multi-scale and multi-physics processes. In particular, we considered the availability of analysis tools for multi-scale models and model-based multi-scale data integration. We provide a compact review of methods for model-based data integration and model-based hypothesis testing. Furthermore, novel approaches and recent trends are discussed, including computation time reduction using reduced order and surrogate models, which contribute to the solution of inference problems. We conclude the manuscript by providing a few ideas for the development of tailored multi-scale inference methods.Comment: This manuscript will appear in the Journal of Coupled Systems and Multiscale Dynamics (American Scientific Publishers

Anomeric O-Functionalization of Carbohydrates for Chemical Conjugation to Vaccine Constructs.

Carbohydrates mediate a wide range of biological interactions, and understanding these processes benefits the development of new therapeutics. Isolating sufficient quantities of glycoconjugates from biological samples remains a significant challenge. With advances in chemical and enzymatic carbohydrate synthesis, the availability of complex carbohydrates is increasing and developing methods for stereoselective conjugation these polar head groups to proteins and lipids is critically important for pharmaceutical applications. The aim of this review is to provide an overview of commonly employed strategies for installing a functionalized linker at the anomeric position as well as examples of further transformations that have successfully led to glycoconjugation to vaccine constructs for biological evaluation as carbohydrate-based therapeutics

Backbone chemical shift assignments of human 14-3-3σ\sigma

14-3-3 proteins are a group of seven dimeric adapter proteins that exert their biological function by interacting with hundreds of phosphorylated proteins, thus influencing their sub-cellular localization, activity or stability in the cell. Due to this remarkable interaction network, 14-3-3 proteins have been associated with several pathologies and the protein-protein interactions established with a number of partners are now considered promising drug targets. The activity of 14-3-3 proteins is often isoform specific and to our knowledge only one out of seven isoforms, 14-3-3$\zeta$, has been assigned. Despite the availability of the crystal structures of all seven isoforms of 14-3-3, the additional NMR assignments of 14-3-3 proteins are important for both biological mechanism studies and chemical biology approaches. Herein, we present a robust backbone assignment of 14-3-3$\sigma$, which will allow advances in the discovery of potential therapeutic compounds. This assignment is now being applied to the discovery of both inhibitors and stabilizers of 14-3-3 protein-protein interactions

Development of a Low-Cost Platform for 3D Bioprinting Applications

Due to the fast pace advancements in 3D printing technologies, it is now possible to bring to life three-dimensional models designed on a computer. The growing availability of user-friendly, high-resolution printers, presents us with the opportunity to adapt this tool for multiple biological purposes. Our aim is to develop a mechanism on a customized commercial 3D printer to deliver a hydrogel material to act as a scaffold for cell proliferation. Compared with non-biological printing, 3D bioprinting involves several complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical hurdles related to the sensitivities of living cells and the formation of tissues. The modified 3D printer efficiently delivers biological ink substances such as alginate, collagen, chitosan, gelatin, and fibrin to create a biocompatible scaffold that will host cell proliferation. The scaffold can then be suspended in a solution with a cell line to initiate cell differentiation and self-assembly of the selected tissue. The project will allow for a cheaper more effective strategy for class research projects, medical drug testing, disease research, and potentially tissue/organ implantation. Establishing a functional platform and experimenting with the bioprinting of cartilage and other tissues enhances our understanding of cell and tissue biology and can have a significant impact in clinical settings. Developing an affordable mechanism will allow this technology to be demonstrated in undergraduate labs for a better understanding of how engineering tools can be applied to solve biological problems

Far-from-equilibrium transport with constrained resources

The totally asymmetric simple exclusion process (TASEP) is a well studied example of far-from-equilibrium dynamics. Here, we consider a TASEP with open boundaries but impose a global constraint on the total number of particles. In other words, the boundary reservoirs and the system must share a finite supply of particles. Using simulations and analytic arguments, we obtain the average particle density and current of the system, as a function of the boundary rates and the total number of particles. Our findings are relevant to biological transport problems if the availability of molecular motors becomes a rate-limiting factor.Comment: 14 pages, 7 figures, uses iopart12.clo and iopart.cl