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Synthetic biology E. coli strain development for expression of functional human GPCRs with roles in human disease

Award Number: R43GM126828
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract G protein-coupled receptors (GPCRs) mediate most of our body's physiological responses to hormones, neurotransmitters and environmental stimulants. They are trans-membrane proteins that are expressed in every type of cell in the body where their function is to detect molecules outside the cell and transmit signals across the membrane to activate cellular responses. These proteins are involved in many diseases and present a wide range of opportunities as therapeutic targets in areas including diabetes, cancer, central nervous system disorders, inflammation, and pain. GPCRs have been and will remain among the most important targets of drug discovery in the pharmaceutical industry. In order to have sufficient and functional GPCR proteins for drug screening, an efficient heterologous protein expression system is required. The current heterologous expression systems using insect cells or mammalian cells typically result in low yields and require lengthy molecular biology efforts. E. coli is a very attractive protein expression system which offers flexibility in genetic manipulation, rapid growth, ease of scaling up and very low cost. However, current E. coli strains are limited in their ability to produce fully functional GPCR proteins. In this project, Primordial Genetics aims to develop a novel E. coli strain for producing functional GPCRs by a patented synthetic biology technology called Function Generator™. This technology has previously been applied to E. coli to generate functionality that cannot be created by classical genetic approaches. We propose to screen our combinatorial expression libraries to discover all the genes involved in improved expression of GPCRs. The expression of six well-known GPCRs will be validated by biochemical assays and function assays. At the end of this Phase I project, we will have demonstrated that for each target GPCR we have at least one FG gene that enables high-level expression of the soluble GPCR. Our Phase II project will comprise further strain development by stacking the trait genes to have a robust E. coli strain that is universally useful for GPCR production. The E. coli production host can be licensed to pharmaceutical companies and can be used to supply the market with GPCRs for functional screening. This endeavor not only bears great business prospects but also provides the scientific community with valuable R&D resources.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	PRIMORDIAL GENETICS INC.	3550 GENERAL ATOMICS COURT MS G02 400	SAN DIEGO	CA	92121	SAN DIEGO	USA	Biomedical Research and Research Training	000	1	12/14/2018	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $224,952 )
2018	2018	PRIMORDIAL GENETICS INC.	3550 GENERAL ATOMICS COURT MS G02 400	SAN DIEGO	CA	92121	SAN DIEGO	USA	Biomedical Research and Research Training	000	1	12/25/2017	NEW	$224,952
														Subtotal = $224,952

Grand Total All Awards = $224,952

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Synthetic biology E. coli strain development for expression of functional human GPCRs with roles in human disease

Award Number: R43GM126828

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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