Search Results for: cell signalling
Chromatin dynamics involved in gene regulation
There is a growing interest in manipulating chromatin dynamics for applications in cell signalling, drug discovery and chromatin research. Progress in this area requires the identification of design rules for the chromatin system.
DNA in cells is wrapped around proteins called histones forming structures known as nucleosomes. These nucleosomes can fold into higher ordered structures, concealing DNA within them. This reduces accessibility to the DNA and adds another layer to the regulation of gene expression. This is a new target for drug discovery.
Opening of these structures to expose the DNA is influenced, among other factors, by gene expression levels. The deregulation of gene expression levels could be responsible for many diseases possibly because proteins in charge of the burial of DNA in the nucleosomes are themselves deregulated. Studying these potential changes in gene expression without altering the underlying DNA sequence is known as Epigenetics, an actively expanding research field.
The Ras-Raf-MEK-ERK Pathway is an important cell signalling route with many implications for cancer biology and therapeutic development. Dis-regulation of some of this pathway’s proteins expression and phosphorylation status are observed in about one-third of all human cancers. Access to specific tools to study this pathway is essential to a better understanding of its role in cancer for novel drug development. If you are working on this topic, you’ll be interested in taking a look at the range of reagents on offer for a wide variety of applications.
The mitogen-activated protein kinase (MAPK) signaling pathway is activated by a number of extra and intracellular stimuli including cytokines, growth factors, and hormones as well as stressors such as oxidative and ER stress. This pathways plays a key role in the regulation of many cellular processes including proliferation, differentiation, the stress response, motility, growth, differentiation, survival, and death. Abnormal MAPK signaling may contribute to increased or uncontrolled cell proliferation and/or resistance to apoptosis. To study this complex pathway, several tools are available, from the pathway specific arrays for an initial screen, to phospho-specific ELISA tests for individual target validation. This post aims at helping you to easily identify tools to explore this pathway in your samples (from arrays to phospho-ELISAs). However, I could not start without showing you once more one of these eye-catching illustrations of cell signalling pathways. I’ll let you explore it to dig out the MAPK protein cascade among all of them (a kind of Where’s Wally for the researcher !).
Immunotherapy represents a field in Drug Discovery which is quickly developing and leading to significant progress in treatments of a number of diseases, especially cancer. The approach is based on inducing, enhancing, or surpressing an immune response. Therapeutic manipulation of immunopathways has led to promising clinical results . The first therapeutic antibodies directed against the checkpoint receptor PD-1 have been already brought to the market (Nivolumab, Pembrolizumab) by Bristol Myers Squibb and Merck/MSD respectively, and approved for the treatment of diverse cancer types.
Today, I would like to review tools to build up a comprehensive assay set up for cell based inhibitor screening on PD-1 / PD-L1/PD-L2 binding. [Read more…]
The treatment of diseases by inducing, enhancing, or surpressing an immune response is referred to as Immunotherapy. Therapeutic manipulation of immunopathways has led to promising clinical results for the treatment of a number of diseases. The first therapeutic antibodies directed against the checkpoint receptor PD-1 have been already brought to the market (Nivolumab, Pembrolizumab) by Bristol Myers Squibb and Merck/MSD respectively, and approved for the treatment of diverse cancer types.
Today, I would like to review a versatile tool to conduct cell based inhibitor screenings on PD-1 / PD-L1/PD-L2 binding. [Read more…]
Cell-Based ELISA tests now enable precise measurement of the phosphorylation status or expression profiles of target proteins (biomarkers) in whole cells. In this post, a review of high performing cell-based assays is made.
As discussed previously in our recent Drug Discovery post, Immunotherapy is one of the central research fields for various disease treatments and also certain cancers. A major regulator of immune homoeostasis and preventing autoimmunity, but potentially dysregulated in various cancers, Immune Checkpoint targeting has already led to promising treatment molecules (Nivolumab, Pembrolizumab…).
To face the challenges of Immune system complexity and the tumor microenvironment, BPS Biosciences have developed several reporter cellular lines (the full listing is here) to complement Biochemical assays. By providing more physiological outcomes in a cellular context (functionality of the whole cell signaling pathway) BPS cell lines allow, for example, the identification of an agonist vs antagonistic effect of your candidate. [Read more…]
PD-1:PD:-L1 immune checkpoint pathway targeting immunotherapies have shown great potential for many cancer patients. Recently, The FDA has granted accelerated approval to the immunotherapy drug pembrolizumab (Keytruda® – humanized monoclonal IgG4 antibody against human cell surface receptor PD-1) for use in some patients with advanced gastric stomach cancer (see NIH-NCI news). However, response to these treatments is not guaranteed for each patient. With the complexity of the immune system and tumour microenvironment, providing more physiological outcomes for immunotherapies is necessary. Biochemical assays alone cannot consider the functionality of the whole cell signalling pathway. Complementing them with cell-based assays provides a comprehensive approach for identifying and developing new and improved immunotherapy treatments. Cellular line engineering has simplified and accelerated the development of such immunoassays. Targets have been chosen from both immune activators and suppressors with the aim of obtaining precise control of the immune system.
BPS Bioscience have engineered 6 cellular lines, turning them into cell-based reporter assays for Human Immune Checkpoint research. I’d like to present a summary of how each cellular line functions.