Antibody Recognition of Cancer Cells via Glycan Surface Engineering

Stimulation of the body's immune system toward tumor cells is now well recognized as a promising strategy in cancer therapy. Just behind cell therapy and monoclonal antibodies, small molecule-based strategies are receiving growing attention as alternatives to direct immune response against tumor cells. However, the development of small-molecule approaches to modulate the balance between stimulatory immune factors and suppressive factors in a targeted way remains a challenge. Here, we report the cell surface functionalization of LS174T cancer cells with an abiotic hapten to recruit antibodies to the cell surface. Metabolic glycoengineering followed by covalent reaction with the hapten results in antibody recognition of the target cells. Microscopy and flow cytometry studies provide compelling evidence that metabolic glycoengineering and small molecule stimulators can be combined to direct antibody recognition. Keywords: antibody; bioorganic chemistry; cancer; chemical biology; glycoengineerin

Identification of molecular integrators shows that nitrogen activelycontrolsthephosphatestarvationresponseinplants

Nitrogen (N) and phosphorus (P) are key macronutrients sustaining plant growth and crop yield and ensuring food security worldwide. Understanding how plants perceive and interpret the combinatorial nature of these signals thus has important agricultural implications within the context of (1) increased food demand, (2) limited P supply, and (3) environmental pollution due to N fertilizer usage. Here, we report the discovery of an active control of P starvation response (PSR) by a combination of local and long-distance N signaling pathways in plants. We show that, in Arabidopsis (Arabidopsis thaliana), the nitrate transceptor CHLORINA1/NITRATE TRANSPORTER1.1 (CHL1/NRT1.1) is a component of this signaling crosstalk. We also demonstrate that this crosstalk is dependent on the control of the accumulation and turnover by N of the transcription factor PHOSPHATE STARVATION RESPONSE1 (PHR1), a master regulator of P sensing and signaling. We further show an important role of PHOSPHATE2 (PHO2) as an integrator of the N availability into the PSR since the effect of N on PSR is strongly affected in pho2 mutants. We finally show that PHO2 and NRT1.1 influence each other’s transcript levels. These observations are summarized in a model representing a framework with several entry points where N signal influence PSR. Finally, we demonstrate that this phenomenon is conserved in rice (Oryza sativa) and wheat (Triticum aestivum), opening biotechnological perspectives in crop plants.This work was supported in the Honude group (Biochemistry & Plant Molecular Physiology) by Agence Nationale de la Recherche (IMANA ANR-14-CE19-0008 with a doctoral fellowship to A.S.), by the Centre National de la Recherche Scientifique (CNRS LIA-CoopNet to G.K.), and by the National Science Foundation (NSF IOS 1339362-NutriNet). Research in V.R.’s laboratory was funded by the Ministry of Economy and Competitiveness and AEI/FEDER/European (grants BIO2013-46539-R and BIO2016-80551-R)

"Active surfaces" as Possible Functional Systems in Detection and Chemical (Bio) Reactivity

This article presents design strategies to demonstrate approaches to generate functionalized surfaces which have the potential for application in molecular systems; sensing and chemical reactivity applications are exemplified. Some applications are proven, while others are still under active investigation. Adaptation and extension of our strategies will lead to interfacing of different type of surfaces, specific interactions at a molecular level, and possible exchange of signals/cargoes between them. Optimization of the present approaches from each of five research groups within the NCCR will be directed towards expanding the types of functional surfaces and the properties that they exhibit

Power and limitations of electrophoretic separations in proteomics strategies

Proteomics can be defined as the large-scale analysis of proteins. Due to the complexity of biological systems, it is required to concatenate various separation techniques prior to mass spectrometry. These techniques, dealing with proteins or peptides, can rely on chromatography or electrophoresis. In this review, the electrophoretic techniques are under scrutiny. Their principles are recalled, and their applications for peptide and protein separations are presented and critically discussed. In addition, the features that are specific to gel electrophoresis and that interplay with mass spectrometry (i.e., protein detection after electrophoresis, and the process leading from a gel piece to a solution of peptides) are also discussed

Multiscale modelling of auxin transport in the plant-root elongation zone

In the root elongation zone of a plant, the hormone auxin moves in a polar manner due to active transport facilitated by spatially distributed influx and efflux carriers present on the cell membranes. To understand how the cell-scale active transport and passive diffusion combine to produce the effective tissue-scale flux, we apply asymptotic methods to a cell-based model of auxin transport to derive systematically a continuum description from the spatially discrete one. Using biologically relevant parameter values, we show how the carriers drive the dominant tissue-scale auxin flux and we predict how the overall auxin dynamics are affected by perturbations to these carriers, for example, in knockout mutants. The analysis shows how the dominant behaviour depends on the cells' lengths, and enables us to assess the relative importance of the diffusive auxin flux through the cell wall. Other distinguished limits are also identified and their potential roles discussed. As well as providing insight into auxin transport, the study illustrates the use of multiscale (cell to tissue) methods in deriving simplified models that retain the essential biology and provide understanding of the underlying dynamics

Etude par dichroisme circulaire et par marquage isotopique des interactions de l'amphotericine B et de ses derives avec les erythrocytes humains et leurs membranes isolees

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Identification of 14kDa auxin-binding proteins in a tobacco plasma membrane subfraction responsive to auxin

International audienc

On-cell catalysis by surface engineering of live cells with an artificial metalloenzyme

Metal-catalyzed chemical transformations performed at the cellular level bear great potential for the manipulation of biological processes. The complexity of the cell renders the use of transition metal chemistry difficult in cellular systems. The delivery of the reactive catalyst and the control of its spatial localization remain challenging. Here we report the surface functionalization of the unicellular eukaryote Chlamydomonas reinhardtii with a tailor-made artificial metalloenzyme for on-cell catalysis. The functionalized cells remain viable and are able to uncage a fluorogenic substrate on their surface. This work leverages cell surface engineering to provide live cells with new-to-nature reactivity. In addition, this operationally simple approach is not genetically encoded and thereby transient, which offers advantages with regard to temporal control, cell viability, and safety. Therefore, and as a feature, the movement of the functionalized cells can be directed by light (via phototaxis), allowing for the three-dimensional localization of catalysts by outside stimuli