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A functional genomics tool for high throughput cell free analysis of regulatory components

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43HG009988-01
Agency Tracking Number: R43HG009988
Amount: $275,955.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NHGRI
Solicitation Number: PA16-302
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-09-11
Award End Date (Contract End Date): 2018-12-31
Small Business Information
San Francisco, CA 94107-3007
United States
DUNS: 079761816
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (646) 725-6686
Business Contact
Phone: (646) 725-6686
Research Institution

Project Summary
Here we seek to develop a novel functional genomics tool a RNA Polymerase II dependent RNAPII
eukaryotic cell free expression system that allows for rapid characterization of human regulatory components
There is a pressing need for new tools that can analyze the exponentially increasing amount of genomic data
that has been collected through NHGRI sequencing initiatives and through advances in next generation
sequencing technology Hidden within this genomic data is understanding to causes of human pathology
Understanding genomic data will become increasingly critical as new initiatives such as TOPMed seek to tie
primary data to clinical outcomes
Synvitrobio s technology produces cell free systems that are able to express multiple DNA sequences without
needing to grow cells This allows for x higher throughput analysis at x the time and cost of
equivalent cellular expression The cell free system effectively prototypes a cell They can be thought of as
simplified and open environments to engineer biological complexity while conserving the native cellular milieu
of the originating source The system takes in single or multiple DNA s and conducts transcription and
translation to produce functional protein
We propose developing a RNAPII dependent eukaryotic cell free expression system that is able to prototype a
eukaryotic cell line Current eukaryotic cell free systems are able to conduct either native transcription or
separately native translation but not both simultaneously Both native transcription and native translation are
necessary for the end system to be capable of high throughput functional genomics exploration In the
proposed Phase I feasibility effort we will first demonstrate a HeLa combined nuclear and cytoplasmic cell free
expression system supporting RNAPII dependent native transcription and native translation Aim We will
also demonstrate two examples of gene regulation in a eukaryotic cell free system a RNAPII independent
example of operator repressor binding and a RNAPII dependent example of allele specific gene regulation
Aim The long term Phase II goal is to demonstrate the system s ability to rapidly screen genomic data
going from bioinformatics collection DNA synthesis expression and assay in a day with a demonstration that
collected results mirror expected results from cellular experiments Project Narrative
A functional genomics tool from eukaryotic cell free systems benefits the public by providing a platform that
can rapidly screen and develop functional conclusions from the increasing amount of collected personal and
human genomics data This aids in identifying fundamental underlying mechanisms of associated genetic
variants and related causes of human pathology Understanding genomics data will be critical to developing
personalized disease cures

* Information listed above is at the time of submission. *

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