Site-specific binding of proteins to DNA plays an important role in cell development, cell signaling, the cell cycle, and diseases such as cancer. There are two overarching goals to this proposal: (1) to develop a means for the identification of proteins bound to specific DNA sequences, and (2) to develop a better method for the identification of immunoprecipitation (IP) functional affinity reagents against DNA-bound proteins found on a complex antigen source. We propose to apply the proof-of-principle using the interaction of transcription factors (TFs) and their specific DNA binding sites as a model. TFs are one major example of such DNA-binding proteins. Once bound to their binding site(s), TF proteins can regulate the transcription of genes, thereby making individual genes either more or less active. Although this is a proposal to develop a better means toward obtaining functional affinity reagents against proteins when they are bound to DNA, the method itself can be applied to other uses.

Public Health Relevance

Many DNA-binding proteins are bound to specific DNA sequences and assist to regulate gene expression. Whether activating or repressing gene regulation, these proteins control the transfer of genetic information from DNA to RNA. As one example, transcription factor modulation of target genes leads to new molecules appearing on an immune cell's surface, including receptors for cytokines that stimulate cell proliferation and differentiation. We believe the proposed functional affinity screening method will allow us to more efficiently isolate affinity reagents that can be used to study the complex controlling mechanisms of the genome.

Agency
National Institute of Health (NIH)
Type
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
Project #
1R41DK104602-01
Application #
8830164
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Arreaza-Rubin, Guillermo
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Axiomx, Inc.
Department
Type
DUNS #
City
Branford
State
CT
Country
United States
Zip Code
06405