Genetic jiggery-pokery.

Jul 04 2016

It's long been known that DNA encodes information in a four-bit pattern which can be read and processed like any other bitstream. Four different nucleotides, paired two by two, arranged in one of two configurations side by side by side in a long string of letters, many times longer than the size of the cell containing the full DNA strand. Every cell in every single lifeform contains the same DNA sequence, regardless of what the cell actually does. So how, many have asked, does a cell know if it should help produce hair, or skin, or pigments, or something else? As it turns out, there is more than one layer of information encoding at work in DNA - the way in which DNA is folded in three dimensions also encodes information used by the cell. Inside of every cell the DNA is tightly wound around a cluster of eight proteins called histones, which provide a superstructure to support the two meter long molecule. The question then becomes, how are the specific parts of the DNA molecule directly involved in what a given cell does, called nucleosomes kept accessible to the rest of the cellular machinery? Hypotheses to this effect have been going around since the 1980's but only recently has computational simulation been feasiable to put them to the test. As it turns out, the loops, twists, bends, curves, and folds that DNA undergoes around the histone octomers keep keep those functional nucleosomes exposed so that they can be acted upon. The simulations randomly pushed, pulled, prodded, and twisted virtual DNA strands to see what would happen, and they noted that nucleosomal configurations were in fact impacted. Those simulation results were then verified through laboratory observation of two species of common yeasts. It was also confirmed that point mutations can also influence the folding of DNA, which can result in changes in the frequency of synthesis of proteins due to change in accessibility of those nucleosomes. The entire (highly technical) paper (it gave me a headache on the first readthrough, okay?) is available in its entirity on PLOS ONE under a Creative Commons By Attribution v4.0 International license.

Gene therapy for the win, CRISPr with RNA, and growing telomeres without gene hacking.

Jun 05 2016

The past couple of weeks have brought with them some pretty interesting advances in the field of genetic engineering. So, let's get into it.

The first is, as far as anybody can tell, a working genetic therapy regimen for SCID, or severe combined immunodeficiency syndrome. SCID has long been colloquially referred to as "bubble boy syndrome" after David Vetter was born in 1971.ev with the condition and a movie was released about his life in 1976.ev, due to the fact that children born with the condition utterly lack a functional immune system; the slightest illness is likely to kill them in short order. Of the hundreds of immune disorders that humans can be born with, SCID is interesting in that there are no less than thirteen genetic mutations which can cause simultaneous B- and T-lymphocyte dysfunction. While there have been a number of treatments developed over the years which have met varying degrees of success none of them has been called anything like a cure, let alone a commercially viable one. Pharmaceutical megacorporation GalaxoSmithKline has unveiled Strimvelis, a practical implementation of a gene therapy technique developed at the San Raffaele Telethon Institute for Gene Therapy in Milan that, as far as anybody can tell completely cures SCID. It involves extracting bone marrow from the patient, separating the stem cells from the marrow, and applying a retrovirus that deletes the defective gene and replaces it with a corrected sequence of base pairs. The modified stem cells are then re-inserted into the patient where they pick up production of B- and T-lymphocytes that function normally. Eighteen children over the last fifteen years have undergone treatment with Strimvelis and every one of them no longer show signs of being afflicted with SCID, a helpful sign if I ever saw one but, as with many things, guardian optimism is the way to go. Advisors in the EU formally recommended that Strimvelis go on the market in April, and there are reportedly plans on the desktop for seeking US approval in 2017.ev. Suffice it to say that this is going to kick over a lot of anthills when it hits the market; for a very serious disease this completely breaks the "treat it continually" model of commercial medicine, especially for a rare disease which perhaps one hundred people are born with every year.

It remains anybody's guess how GSK is going to make their projected 14% return on investment on Strimvelis. I'm kind of afraid to see what the price tag is going to be.

Inflatable space station modules, successful gene therapy for aging, and neuromorphic computing.

May 29 2016

Now that I've got some spare time (read: Leandra's grinding up a few score gigabytes of data), I'd like to write up some stuff that's been floating around in my #blogfodder queue for a couple of weeks.

First up, private-sector aerospace engineering and orbital insertion contractor SpaceX announced not too long ago announced that one of their unmanned Dragon spacecraft delivered an inflatable habitat module to the International Space Station. Following liftoff from Cape Canaveral the craft executed a rendezvous with the ISS in low earth orbit, where the ISS' manipulator arm grappled the craft. In addition to supplies and freight necessary for crew and station one of Bigelow Aerospace's inflatable station modules. For a space station peripheral the deflated BEAM (Bigelow Expandable Activity Module) is remarkably small (1,360 kilographs of mass, 1.7 meters long, 2.4 meters in diameter), but when completely filled with atmosphere it grew to a full size of 3.2 meters in length by 4 meters in diameter (I think I got those matched up). The current gameplan is to slowly but carefully inflate but not use the module to see how it acts in microgravity; remember that this has never been attempted before so science is being done at the same time that history is being made. While this seems overly cautious there are good (albeit not well advertised) reasons for this: The phenomenon of outgassing (note: SSL cert was issued by NASA's CA, so your browser probably doesn't trust it), or materials one would expect to be stable beause they're usually on Earth emitting gases that can leave films on surfaces (or are potentially toxic in vivo) was first observed in early photogrammetry satellites. Thus, the experimental module is instrumented, probably to determine whether or not (and if so, how much) the construction materials will outgas while installed; the results will be used to provide data when Bigelow Aerospace designs the next iteration of the BEAM. Outgassing aside (because that's the phenomenon I have the most experience with) NASA and Bigelow are also interested in tracking how the BEAM stands up overall (it's a semiflexible pressurized envelope in a vacuum so how well the seams and structural members hold up are a major concern), how well it withstands micrometeoroid impacts (impacts with space dust, basically), how much radiation makes it inside the module over time (pretty much the big issue if this style of module will ever be used for habitation, to say nothing of experiments being corrupted), and, of course, whether or not it leaks.

At the end of the twenty-four month experiment, the BEAM will be sealed up, detached from the ISS, and jettisoned with the assistance of the MSS, whereupon its orbit will decay and it will eventually burn up upon re-entry.