Summary
Research into the molecular mechanisms of salt-sensitive hypertension, specifically identifying E3-ubiquitin ligases that regulate NKCC2 ubiquitination and their role in NaCl reabsorption and blood pressure.
High salt-dependent regulation of the Na+/K+/2Cl- co-transporter (NKCC2) ubiquitination by E3-ubiquitin ligases in Thick Ascending Limb
US · IL
NIH RePORTER
grant
awarded
#nih-5R03DK140261-02
What they want
The project aims to discover E3-ubiquitin ligases mediating NKCC2 ubiquitination and their role in NaCl reabsorption and blood pressure regulation under normal or high salt diets. It hypothesizes that high salt diet stimulates 48-linked poli-ubiquitination of NKCC2 via multiple E3-ubiquitin ligases. The work will explore the mechanism and signaling cascade by which high-salt diet stimulates NKCC2 ubiquitination and characterize new E3-ubiquitin ligases critical for salt-sensitive hypertension, focusing on specific interactions between E3-ubiquitin ligases and adaptors with NKCC2.
Deliverables
- Increased knowledge on post-translational mechanisms regulating blood pressure
- Understanding of post-translational mechanisms regulating NKCC2 expression
- Identification and characterization of new E3-ubiquitin ligases involved in salt-sensitive hypertension
- Foundational knowledge for developing new strategies and novel, specific loop diuretics for treating salt-sensitive hypertension
Technical requirements
- Study of NKCC2 ubiquitination
- Investigation of E3-ubiquitin ligases and adaptors
- Use of FBXL13-KO mice models
- Analysis of NaCl reabsorption and blood pressure regulation
- Study of 48-linked poli-ubiquitination
Market context
inferred from NAICSR&D in Physical, Engineering, Life Sciences (except Nanotech & Biotech)
NAICS 541715
- US market size
- $95B
- Typical award
- $100K – $50M+
Typical buyers
DoDNSFNIHNASADOE
Commonly required
DCAA-compliant accountingITARCMMC L2
