Therefore, to enable measurement of low expressing and large loss-of-function mutants, it is important to lower the EC50 of the wild type receptor.
Because of the large increase in glutamate sensitivity and a demonstrated lack of coupling between the T6′S mutation and the ligand binding site, we concluded that incorporation of T6′S as a background mutation is appropriate for measuring large loss-of-function mutations in the GluClβ receptor.
Mutation of pore lining residues on the M2 helix of Cys-loop receptors has had dramatic effects on ligand sensitivity, open channel duration, and receptor desensitization in many studies, thereby facilitating measurement of low expressing and large loss-of-function mutations.
More generally, this study also highlights the interest of large scale loss-of-function screens for characterizing the molecular mechanism of action of environmental contaminants.
In our pursuit to uncover novel synthetic lethality targets of the MYC signaling pathway, we conducted a large scale loss-of-function RNAi screen in L-MYC-overexpressing lung fibroblasts and their isogenic controls.
Here we identified 15 genes required for cell growth or proliferation in CD44+CD24- human breast cancer cells in a large-scale loss-of-function screen and found that inhibition of several of these (IL6, PTGIS, HAS1, CXCL3, and PFKFB3) reduced Stat3 activation.
Genome-editing technologies have recently emerged as powerful tools for large-scale loss-of-function studies in zebrafish and will provide new ways to assess tumor suppressor function in zebrafish cancer.
We have carried out a large-scale loss-of-function screen to identify genes that are required by KRAS-transformed colon cancer cells, but not by derivatives lacking this oncogene.
Database URL: http://hts.cancerresearchuk.org/db/public RNA interference (RNAi) is a natural mechanism for gene silencing that is now widely used in large-scale loss-of-function screening campaigns in the form of small-interfering RNA (siRNA) libraries that can be used to knock down genes in a high-throughput manner.
To expand that knowledge we systematically assessed macrophage responses to a large panel of loss-of-function mutants of Mtb.
