Researchers at NIDDK have developed polyclonal antibodies against the G protein, Gbeta5. Gbeta5 is a unique and highly specialized G protein that exhibits much less homology than other Gbeta isoforms (~50%) and is preferentially expressed in brain and neuroendocrine tissue. It is expressed prominently in the neuronal cell membrane, as well as in the cytosol and nucleus. Although this distribution pattern suggests that Gbeta5 may shuttle information between classical G protein-signaling elements at the plasma membrane and the cell interior, its function in the brain is largely unknown.

A capillary-based device and system for measuring the rheological properties of solutions of synthetic and biological polymers. The device automatically serially dilutes and varies the flow rate of a sample, permitting measurement of solution viscosity across wide ranges of concentration and shear rate without changing samples. The device can rapidly and accurately assay solute stability, solute-solvent and solute-solute interactions in solutions of proteins and other macromolecules of biotechnological and pharmaceutical interest, as well as solution injectability.

Researchers at NIH have developed islet beta cell M3 muscarinic acetylcholine receptor knockout mouse. The mice were generated by crossing floxed mouse M3 muscarinic acetylcholine receptor mice with mice in which Cre recombinase was controlled by the beta-cell specific rat insulin promoter (RIP-Cre mice).

Q490L point mutation was introduced into the rat M3 muscarinic receptor cDNA to confer persistent, constitutive (ligand-independent) activity. Expression of the M3 receptor mutant was placed under the control of a 650 bp fragment of the rat insulin promoter II (RIP II) to limit expression to the islet beta cell.

Researchers at NIH have generated transgenic mice in which the M3 muscarinic receptor is overexpressed in pancreatic beta cells. This was done by placing the receptor gene under the control of the 650 bp rat insulin promoter II (RIP II). The resulting mice show a pronounced increase in glucose tolerance and enhanced plasma insulin levels. Strikingly, these mutant mice were resistant to diet-induced glucose intolerance and hyperglycemia.

The cleavage of sphingoid base phosphates by sphingosine-1-phosphate (S1P) lyase to produce phosphoethanolamine and a fatty aldehyde is the final degradative step in the sphingolipid metabolic pathway. Researchers at NIH injected rabbits with the C-terminal peptide of the mouse S1P lyase — 551-TTDPVTQGNQMNGSPKPR-568 — to develop an antibody that can be used in western blotting to study this pathway.

Two isoforms of sphingosine kinase, sphingosine kinase 1 (SphK1) and sphingosine kinase 2 (SphK2), convert sphingosine to sphingosine 1-phosphate (S1P) in mammalian cells. While the importance of SphK1 has been known for some time, information about SphK2 is still being revealed. Therefore, researchers at NIH have developed an antibody against mouse SphK2, which can be used to further understand the role of this enzyme.

The vast majority of people infected with Hepatitis C Virus (HCV) will have chronic infection. Over decades, this can lead to liver disease and liver cancer. In fact, HCV infection is the leading cause of liver transplants in the U.S. Several new drugs have recently come into the market that will likely change the HCV treatment paradigm. However, the effectiveness of these new drugs can vary depending on the HCV genotype. Thus, there is still the need for additional new therapeutics against HCV.

Bag6 (BCL2 associated athanogene 6) is a multifunctional chaperone involved in tail anchored protein biogenesis, endoplasmic reticulum-associated protein degradation, and degradation of mislocalized membrane proteins. It is the central component of a stable three chaperone complex that also contains two cofactors-Ubl4A and Trc35. This complex acts in conjunction with the co-chaperone SGTA to channel proteins bearing an exposed hydrophobic segment in the cytosol to avoid protein aggregation.