Posters

A large percentage of new drugs fail in clinical studies due to cardiac toxicity. Development of highly predictive in vitro assays suitable for screening, safety assessment or other environments is therefore extremely important for drug development. Human cardiomyocytes derived from stem cell sources can greatly accelerate the discovery of cardiac drugs and improve drug safety by offering more clinically relevant cell-based models than those presently available.

The characterization of autoimmune disease-specific biomarkers are of primary importance for the development of diagnostic tools and the comprehension of pathogenetic mechanisms leading to autoimmunity. To this aim a protein microarray was employed to analyze serum samples from patients with autoimmune hepatitis (e.g. AIH & PBC) and of healthy as controls. A panel of autoantigens able to discriminate among the groups of patients was identified for potential use as biomarkers.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations of the CF transmembrane conductance regulator protein (CFTR), a cAMP-regulated chloride channel. One of the most common CFTR mutations is the deletion of phenylalanine in 508 position (DelF508-CFTR). This mutation induces small conformational change hence the CFTR trafficking is no more effective. The main idea is to find a molecule to facilitate the DelF508-CFTR trafficking to the plasma membrane.

Animal venoms and toxins are a rich source of novel biologics with several making the progression from tool to therapeutic such as FDA approved Integrilintm (Eptifibatide) (Millennium pharmaceuticals)1 derived from Rattlesnake venom for unstable angina.

Membrane proteins, such as G-protein-coupled receptors, are known to be much more difficult to purify and crystallise than soluble proteins due to their native environment within the lipid bilayer of the cell membrane. The in meso (lipidic cubic phase or LCP) crystallisation technique has revolutionised the process of crystallising membrane proteins. This method utilises highly viscous lipid mesophases to contain the membrane proteins for crystallisation.

Cell colony formation assays measure a cell's ability to grow unattached to a surface and have applications in a range of areas including hematopoietic stem cell research, cell transformation studies and the prediction of responses of tumors to chemotherapeutic agents. The results of this study demonstrated that Acumen eX3 can be used as a high-throughput platform for investigation of effects of test compounds and RNAi reagents on cell colony formation.

The Acumen eX3 is the fastest imaging system available, collecting and simultaneously analysing over 40 images/second, covering the entire well, without the trade off of having to use lower resolution. Acumen is well established for cell-based high-content screening, but researchers have recently applied its large field of view to rapidly analyse complex cellular or animal models, such as angiogenic tube formation, C. elegans or drosophila larvae.

The conventional antibody screening assay based on antibody-antigen binding has been enzyme-linked immunosorbent assay (ELISA). While tedious and consuming, ELISA has proved sufficient for the identification of antibodies directed against secreted antigens. However, cell surface antigens (e.g. GPCRs) provide challenges for ELISA due to the shortage of soluble antigens and high variability resulting from loss of cells during wash procedures.

The Acumen eX3 can be used to study the process of cellular adhesion, whereby adherent cells types specifically, endothelial cells can be grown to confluence in microtitre plate wells and other cells types e.g. neutrophils added. The neutrophils can be differentially stained with calcein AM and the adhesion profile monitored and quantified. Cell adhesion can be determined simply by correlating retained fluorescence with cell number.