I’ve made ALOT of breakthroughs in my research these past few months; here is a short update on a paper we submitted. More updates on molecular biology coming soon! Cover art is a collage of figures from the paper.

P2X4 receptors, Preprints, and [open access] papers

We submitted this article for publication a few weeks ago, with me as co-first author. I picked up this project last summer and have been working on it ever since. My undergraduate training is in molecular biology/biochemistry, so it was nice to put that training back to use. I personally love structure-function studies, and this one was intense. Xenopus laevis oocytes really are an amazing tool to study ion channels and receptor pharmacology.

My favorite part was getting around the fact that D354R and R33D are “nonfunctional”. Shai Silberberg et al figured out a clever way around this issue when they were studying P2X4Rs  back in the mid-2000s: mix wildtype and nonfunctional mutant RNA, and test for any changes in function, which is likely due to the mutant protein being present in the homomeric receptor (P2X4Rs are trimers).

Another cool Silberberg trick: use ivermectin (IVM), a P2X4 positive allosteric modulator, to see how the P2X4 receptor gating is affected by a mutation. Simulations, based on single channel recordings, show that IVM interacts favorably with the open conformation of P2X4. Therefore, if a mutation significantly changes the ability of IVM to potentiate the P2X4 receptor, then your mutation is likely affecting the receptor gating. Remember that as ion channels, the P2X4 receptor can be open or closed, acting as a “gate” for ions.

I’m a huge proponent of preprint servers and open access journals. A preprint is a body of work that has not yet undergone peer-review, unlike a journal article, which is in its final form. It lets scientists immediately share their work with the scientific community. It’s a double-edged sword, because on the one hand, its not peer-reviewed, but on the other hand, the peer-review process can take months or years. Long times between publication can hurt your chances of getting a grant (i.e. productivity) but at least with a preprint, you can show that you have been working on publishing SOMETHING while you wait for peer-review. Of course, since it’s not peer-reviewed, you have to take it with a grain of salt, although you shouldn’t trust everything in read in journals, as peer-review isn’t fool-proof.

We submitted to journal with an open-access option, so once the paper is published, its available free of charge to anyone; no subscription needed. As publicly funded researchers, it’s our duty to share our findings with everyone, not just institutions/scientists who have the funds to pay for access.

We are also in the process of submitting a second paper soon, finishing a draft of a third, and fleshing out the prospects of a fourth and fifth paper.