Controlling genes by thought, DNA sequencing in 90 minutes, and cellular memory.

24 November 2014

A couple of years ago the field of optogenetics, or genetically engineering responsiveness to visible light to exert control over cells was born. In a nutshell, genes can be inserted into living cells that allow certain functions to be switched on or off (such as the production of a certain hormone or protein) in the presence or absence of a certain color of light. Mostly, this has only been done on an experimental basis to bacteria, to figure out what it might be good for. As it happens to turn out, optogenetics is potentially good for quite a lot of things. At the Swiss Federal Institute of Technology in Zurich a research team has figured out how to use an EEG to control gene expression in cells cultured in vitro and published their results in that week's issue of Nature Communications. It's a bit of a haul, so sit back and be patient...

First, the research team spliced a gene into cultured kidney cells that made them sensitive to near-infrared light, which is the kind that's easy to emit with a common LED (such as those in remote controls and much consumer night vision gear). The new gene was inserted into the DNA in a location such that it could control the synthesis of SEAP (secreted embryonic alkaline phosphatase; after punching around for an hour or so I have no idea what it does). Shine IR on the cell culture, they produce SEAP. Turn the IR light off, they stop. Pretty straightforward as such things go. Then, for style points, they rigged an array of IR LEDs to an EEG such that, when the EEG picked up certain kinds of brain activity in the researchers the LEDs turned on, and caused the cultured kidney cells to produce SEAP. This seems like a toy project because they could easily have done the same thing with an SPST toggle switch that cost a fraction of a Euro; however, the implications are deeper than that. What if retroviral gene therapy was used in a patient to add an optogenetic on/off switch to the genes that code for a certain protein, and instead of electrical stimulation (which has its problems) optical fibres could be used to shine (or not) light on the treated patches of cells? While invasive, that sounds rather less invasive to me than Lilly-style biphasic electrical stimulation. Definitely a technology to keep a sensor net on.

A common procedure during a police investigation is to have a cheek swab taken to collect a DNA sample. Prevailing opinions differ - personally, I find myself in the "get a warrant" camp but that's neither here nor there. Having a DNA sample is all well and good but the analytic process - actually getting useful information from that DNA sample - is substantially more problematic. Depending on the process required it can take anywhere from hours to weeks; additionally, the accuracy of the process leaves much to be desired because, as it turns out, collision attacks apply to forensic DNA evidence, too. So, it is with some trepidation that I state that IntegenX has developed a revolutionary new DNA sequencer. Given a DNA sample from a cheek swab or an object thought to have a DNA sample on it (like spit on a cigarette butt or a toothbruth) the RapidHIT can automatically sequence, process, and profile the sample using the most commonly known and trusted laboratory techniques today. The RapidHIT is also capable of searching the FBI's COmbined DNA Indexing System (CODIS) for positive matches. Several aspects of the US government are positioning themselves to integrate this technology into their missions, but CEO of IntegenX Robert Schueren claims that the company does not know how their technology is being applied. In areas of the United States widely known to be hostile if one looks as if they "aren't from these parts" RapidHIT has been just that, and local LEOs are reported quite happy with their new purchases. Time will show what happens, and what the aftershocks of cheap and portable DNA sequencing are.

Most living things on Earth that operate on a level higher than that of tropism seem to possess some form of memory that records environmental encounters and influences the organism's later activities. There are some who postulate that some events may be permanently recorded in one's genome, phenomena variously referred to as genetic memory, racial memory, or ancestral memory though the evidence is scant to null supporting these assertions. When you get right down to it, it's tricky to edit DNA in a meaningful way that does't destroy the cells so altered. On those notes, I find it very interesting that a research team at MIT in Cambridge seems to have figured out a way to go about it, though it's not a straightforward or information-dense process. The process is called SCRIBE (Synthetic Cellular Recorders Integrating Biological Events) and makes it possible for a cell to modify its own DNA in response to certain environmental stimuli. The team's results were published in volume 346, issue number 6211 of Science, but I'll summarize the paper here. In a culture of e.coli bacteria a retron (weird little bits of DNA covalently bonded to bits of RNA which code for reverse transcriptases (enzymes that synthesize DNA using RNA as code templates) that are not found in chromosomal DNA) was installed that would produce a unique DNA sequence in the presence of a certain environmental stimulus, in this case the presence of a certain frequency of light. When the bacteria replicated (and in so doing copied their DNA) the retron would mutate slightly to make another gene that coded for resistence to a particular antibiotic more prominent. At the end of the experiment the antibiotic in question was added to the experimental environments; cells which had built up a memory store of exposure to light were more resistent to the antiobiotic. Prevalence of the antibiotic resistence gene was verified by sequencing the genomes of the bacterial cultures. At this time the total cellular memory provided by this technique isn't much. At best it's enough to gauge in an analog fashion how much of or how long something was present in the environment or not but that's about it. After a few years of development, on the other hand, it might be possible to use this as an in vivo monitoring technique for measuring internal trends over time (such as radiation or chemical exposure). Perhaps farther down the line it could be used as part of a syn/bio computing architecture for in vitro or invo use. The mind boggles.