Author Archives: WYSIWYG

Final Project: Bharat Ravi – Regulation of transcription by G-quadruplexes

G-Quadruplexes (GQ) are nucleic acid super-secondary structures forming at G rich regions with a (G2+N1-5 )2+ motif. GQs consist of stacked quartets that are in turned formed by Hoogsteen hydrogen bonded Guanines, and are stabilized by potassium (and sodium) ions. GQs were initially discovered in telomeric sequences but later studies showed their enrichment in promoter and other geneic regions (Du et al., 2007; Lam et al., 2013). Their high enrichment in these regions of the genome suggests that they could play a role in gene regulation. However, most studies on quadruplexes have been done in-vitro especially with respect to their biophysical aspects. Even though GQs have been suggested to influence gene regulation, this possibility has not been thoroughly explored.

I explore the potential effects of GQs on transcription using mathematical models. I have used both deterministic model and stochastic model to study the transcription dynamics in the presence or absence of GQ. In both the models it has been assumed that GQs are downstream of the RNA polymerase binding site and four cases have been explored:

  1. No quadruplex
  2. Quadruplex in template strand
  3. Quadruplex in non-template strand
  4. Quadruplex in both the strands

Most parameters used in the model are adapted from the values reported by biophysical studies, while others have been assumed from guesses.

The models prove that G-quadruplexes can indeed regulate transcription. Future studies would include studying the effect of different parameters on the system and to perform experiments to validate the model.

Advertisements

Project Idea: Noisy gene expression resulting from G-Quadruplexes – Bharat Ravi [Weinberg]

G-quadrulexes are nucleic acid super-secondary structures formed by four strands (intra/intermolecular). The Guanines in the different strands interact by Hoogsteen type hydrogen bonding.  G-quadruplexes forming sequences are found in geneic regions and experiments using immunoprecipitations have validated this prediction. These DNA regions can alternate between quadruplex and duplex structures. Quadruplex structure can impede the elongation of transcription. I aim to use stochastic modeling to predict if quadruplexes can give rise to gene expression noise. Improvisations in the model will include studying transcription bursts and studying the effect of RNA quadruplexes in the translation process.

AUTO Bifurcation Analysis Package in MATLAB

There is a module called Dynamical Systems Toolbox which you can install to do usual non-linear analysis such as bifurcations.

It is free as well.

Image

Funny exercise from Strogatz’s book

Funny exercise from Strogatz's book

Image

Bharat Ravi, IIT Bombay/CSIR-IGIB Delhi

picture1