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Writer's pictureKirk Hartley

Everything Is Open – Assume Nothing – Baselines Change

Day after day, researchers press forward and expand our collective knowledge of molecular biology. Why does it matter to lawyers and risk managers? Consider this – suppose your company sells a chemical that is known to reach the gene that leads to production of Interleukin-10(IL-10), a protein that moderates other immune system cells. Suppose also that testing was done (a big assumption) and the conclusion was that the chemical did not change the sequence of the gene’s nucleotides (the A,C,T,G building blocks of life). Safety, right?

Not so much. Now, ScienceDaily brings news that researchers have shown yet another example of epigenetic changes that render genes more or less accessible to external influence, without altering the sequence of the nucleotides. In this instance, experiments show that gene accessibility varies with amount of and timing of cell cycle replications. More specifically, after confronting an infection, cells cycled through their processes more rapidly to proliferate more cells. And, now we know that when that happens, the gene driving production of IL-10 becomes more accessible. When? Well of course, it’s at day 3.5 of proliferation, in mice. Was your company’s test that specific? Is your company aware of this new data? Is your company about t0 start new tests based on this new knowledge? If not, are the company and its directors exposing themselves to “Caremark” and other lawsuits for failure to have processes in place to monitor scientific changes relevant to the products and processes used by your company?

Back to the science. How do researchers figure these things out? It’s complicated but also simple in a way – comparison matters greatly, as explained below in quotes from the story:

They found [the result] by comparing the genome-wide conformation of DNA in NK cells before and after proliferation in infected mice. They found that in NK cells that hadn’t undergone the proliferation process, the gene for IL-10 was tightly wrapped up and inaccessible for expression. Post-proliferation cells had IL-10 genes that were more open and accessible for expression.

Because the epigenetic study looked at the broader genome of NK cell DNA, not just at the IL-10 gene, Tarrio added, the researchers can now go back to the data to look for other proliferation-induced changes. That could tell them whether proliferation perhaps alters other important functions in NK cells. “It’s entirely likely there are other changes going on and it could be for other purposes,” Tarrio said. “This is one answer to why NK cells proliferate.” With her first grad school paper now published, Tarrio is continuing the research with Biron. The next question in her thesis work will be how long post-infection proliferation and any associated functional changes persist in the NK cells.” (emphasis added)

The full article is:  M. L. Tarrio, S.-H. Lee, M. F. Fragoso, H.-W. Sun, Y. Kanno, J. J. O’Shea, C. A. Biron. Proliferation Conditions Promote Intrinsic Changes in NK Cells for an IL-10 Response. The Journal of Immunology, 2014; DOI: 10.4049/jimmunol.1302999

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