“DNA is like a computer program but far, far
more advanced than any software ever created.” -Bill Gates
DNA computing has recently emerged as an alternative computing
medium. With its intrinsic ability to confine a plethora of logic gates in
nanoscale volumes and its remarkable capabilities in parallel processing,
it is considered as one of the most promising alternatives to classical computing. DNA
strand displacement (DSD) is a method of DNA computation that has
risen as a robust and orthogonal method to perform such tasks.
As such, we have striven to deploy DSD towards quantifying biological
phenomena such as DNA-Protein interactions.
Introducing POSEIDON...
We present POSEIDON, a DNA-induced computational method driven towards a novel approach to a quantitative Transcription Factor (TF) characterization. A molecular algorithm programmed to meticulously examine the affinity of protein-DNA interactions and quantify their concentration in a cell-free sample.
Toolkit's function
To make our system cost-effective and user-friendly, we designed programmable DSD gates derived from plasmid DNA. We programmed an orthogonal formal Chemical Reaction Network (CRN) who's logic gates consist entirely of nicked double- stranded DNA, which makes them uniquely compatible with plasmid DNA as a starting material. Moreover, plasmid derived gates have the advantage of providing highly pure DNA that can easily be replicated and stored into bacterial glycerol stocks and reused a plethora of times.
Proof of concept
The transcription factors that were selected as a proof of concept for our project are associated with melanoma cancer. To validate our process, we tested our method with already validated results from other well-characterized TFs such as NF-kB and ELK1 that play a pivotal role in metastatic conversion.
Filling the Gap
Until now, the information regarding the transcription factors has been based on in silico predictions derived from implied associations. Those predictions come from shared protein motifs with other factors and computer simulations. Consequently, we can infer their binding sites from those predictions and produce the most accurate binding sites.
POSEIDON’s impact on society
POSEIDON contributes to society by facilitating the work of the scientific community. By providing scientists with a universal and cost-effective method which can measure the binding affinity of a certain DNA sequence to a Transcription Factor or Complex, we give them an extra tool for the study of diseases and the testing of drugs targeting transcription factors.