New paper in Cell

 2018 Dec 10. pii: S0092-8674(18)31518-6. doi: 10.1016/j.cell.2018.11.026. [Epub ahead of print]

Intrinsic Dynamics of a Human Gene Reveal the Basis of Expression Heterogeneity.

Abstract

Transcriptional regulation in metazoans occurs through long-range genomic contacts between enhancers and promoters, and most genes are transcribed in episodic “bursts” of RNA synthesis. To understand the relationship between these two phenomena and the dynamic regulation of genes in response to upstream signals, we describe the use of live-cell RNA imaging coupled with Hi-C measurements and dissect the endogenous regulation of the estrogen-responsive TFF1 gene. Although TFF1 is highly induced, we observe short active periods and variable inactive periods ranging from minutes to days. The heterogeneity in inactive times gives rise to the widely observed “noise” in human gene expression and explains the distribution of protein levels in human tissue. We derive a mathematical model of regulation that relates transcription, chromosome structure, and the cell’s ability to sense changes in estrogen and predicts that hypervariability is largely dynamic and does not reflect a stable biological state.

KEYWORDS:

RNA; chromosome; estrogen; fluorescence; heterogeneity; imaging; live-cell; single-molecule; steroid; transcription

PMID: 30554876

 

DOI: 10.1016/j.cell.2018.11.026

Mosquito experiment concluded

It’s hard to see from the photo but when I checked my bucket after a week away, there were definitely a few mosquito larvae swimming around. There was also an impressive biofilm on the bottom of the bucket. It took less than a month for mosquitoes to breed in a newly formed pool of stagnant water. My son also noticed that a nearby flower pot with water only a few centimeters deep also had larvae. So the claims that mosquitos will breed in tiny amounts of stagnant water is true.IMG_3158

Mosquito update

IMG_2917It’s been about two weeks since I first set out my bucket, although I had to move it to a less obtrusive location. Still no signs of mosquito larvae, although judging from my bite frequency even with mosquito repellant, mosquito activity is still high in my garden. I see the occasional insect trapped (they are not really floating since at their size water is highly viscous) in the surface and there is a nice collection of plant debris at the bottom. The water level seems a little bit higher. It has rained at least once every two days since my first post although it has also been very hot so the input seems mostly balanced by the evaporative loss. I’m starting to believe that mosquitos have their prefered gestation grounds that they perpetually use and only exploit new locales when necessary.

Audio of SIAM talk

Here is an audio recording synchronized to slides of my talk a week and a half ago in Pittsburgh. I noticed some places where I said the wrong thing such as conflating neuron with synapse.  I also did not explain the learning part very well. I should point out that we are not applying a control to the network.  We train a set of weights so that given some initial condition, the neuron firing rates follow a specified target pattern. I also made a joke that implied that the Recursive Least Squares algorithm dates to 1972. That is not correct. It goes back much further back than that. I also take a pot shot at physicists. It was meant as a joke of course and describes many of my own papers.

Arsenic and Selenium

You should listen to this podcast from Quirks and Quarks about how University of Calgary scientist Judit Smits is trying to use selenium rich lentils from Saskatchewan, Canada to treat arsenic poisoning in Bangladesh. Well water in parts of rural Bangladesh have high levels of natural arsenic and this is a major health problem. Professor Smits, who is actually in the department of veterinary medicine, has done work using arsenic to treat selenium poisoning in animals. It turns out that arsenic and selenium, both of which can be toxic in high doses, effectively neutralize each other. They each seem to increase excretion of the other into the bile. So she hypothesized that selenium might counter arsenic poisoning but the interaction is nontrivial so it is not a certainty that it would work. Dr. Smits organized a study to transport ten tons of lentils from Canada to Bangladesh this past summer to test the hypothesis and you can hear about the trials and tribulations of getting the study done. The results are not yet in but I think this is a perfect example of how cleverness combined with determination can make a real difference. This study is funded entirely from Canadian sources but it sounds like something the Gates and Clinton foundations could be interested in.

2016-9-26. Corrected a typo, changed Saskatchewan to Bangladesh