Monday, July 18, 2016

Alex Larson, Entry #4, Feeling ever more comfortable

So on Thursday afternoon of last week our Primers finally came in. Unfortunately, since they came in a small cardboard envelope they were easily misplaced and Adam and I had to run all over the building that afternoon to try to find it. Turns out that a member of our lab took it over to her bench because she thought it was for her. On Friday Adam taught me how to rehydrate the primers since they are shipped in a form without water. Earlier in the week we were supposed to go over to the old building and grab some fresh A549 cells (adenocarcinomic human alveolar basal epithelial cells) for DNA extraction to use as the template for PCR. We use A549 cells because our lab has a ton of these cells since they provide good mediums for which we can grow the influenza virus, plus the 45S gene we are looking for is still present and functioning in those cells. It wasn’t until Friday, however, that we were able to get those cells so instead of rushing the extraction, Adam decided to dig through the freezer and find some old A549 DNA and use that instead. Adam later left me in charge of picking the polymerase and the settings for the thermal cycler. After a little research on my own (Adam let me be in charge here), I decided to use the Q5 High-Fidelity Mastermix because it contained basically every component necessary except the primers and template while also being 100 times for accurate than Taq polymerase. So after a lot of tedious benchwork, we were able to create 45S PCR amplicons.
            We later ran our amplicons on a gel, and the amplicons that turned up with bands were subsequently sent off for sequencing. In total, 14 amplicons (though some were of the same amplicon, just a different primer) were sent off, and of those 14, none were sequenced successfully. A lot of the results did have partial sequences though, so when we ran the sequences by NCBI, in virtually all instances where there was a sequence to use, the resulting region of genomic DNA was somewhere in the 45S gene. So while a lot of red color might have turned up on the results page of the sequencing website, we were able to confirm that the region of DNA sequenced was the same region we wanted to sequence. To get full readings and better results, Adam and I are looking into different parameters for PCR and perhaps a different method of sequencing. This is very specific to our overarching DASH project. Our next step is to use this sequence information and amplicons to design single-guideRNA for CRISPR/CAS9 which should snip out the regions within the 18S, 5.8S, and 28S Genes that are not variable leaving us with the ability to see how the variable regions within the entire 45S gene on a whole function.

            On a side note, Dr. Ghedin has been out of the lab on vacation for the past 2 weeks so our entire lab decided to play hooky and go hiking Bull Hill in Cold Spring, New York last Wednesday (7-13). Adam was the one who orchestrated everything because he grew up in Rockland County. We all met at Grand Central and took MetroNorth up to Cold Spring. From there, the 12 of us who went embarked on a 4 hour hike up and down this very steep mountain that had gorgeous views of the Hudson Valley. It was nice to be able to finally get to see members of my lab whom I only occasionally talk to anyway outside the laboratory setting. Plus we were all able to bond about the tortures of walking uphill under a bright sun in high 80 degree temperature. The views certainly made the hike worthwhile though, and I did have the best shower and sleep of my life when I got home that night.     
(Results of our 45S PCR amplicons on a gel)
(Top of Bull Hill)

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