>Well, this week has been exciting. The house sale competed last night, with only a few hiccups. Both us and the seller of the house we were buying got low-ball offers during the week, which provided the real estate agents lots to talk about, but never really made an impact. We had a few sleepless nights waiting to find out of the seller would drop our offer and take the competing one that came in, but in the end it all worked out.
On the more science-related side, despite the fact I’m not doing any real work, I’ve learned a lot, and had the chance to talk about a lot of ideas.
There’s been a huge ongoing discussion about the qcal values, or calibrated base call scores that are appearing in Illumina runs these days. It’s my understanding that in some cases, these scores are calibrated by looking at the number of perfect alignments, 1-off alignments, and so on, and using the SNP rate to identify some sort of metric which can be applied to identify an expected rate of mismatched base calls. Now, that’s fine if you’re sequencing an organism that has a genome identical to, or nearly identical to the reference genome. When you’re working on cancer genomes, however, that approach may seriously bias your results for very obvious reasons. I’ve had this debate with three people this week, and I’m sure the conversation will continue on for a few more weeks.
In terms of studying for my comprehensive exam, I’m now done the first 12 chapters of the Weinberg “Biology of Genomes” textbook, and I seem to be retaining it fairly well. My girlfriend quizzed me on a few things last night, and I did reasonably well answering the questions. 6 more days, 4 more chapters to go.
The most interesting part of the studying was Thursday’s seminar day. In preparation for the Genome Sciences Centre’s bi-annual retreat, there was an all-day seminar series, in which many of the PIs spoke about their research. Incidentally, 3 of my committee members were speaking, so I figured it would be a good investment of my time to attend. (Co-incidentally, the 4th committee member was also speaking that day, but on campus, so I missed his talk.)
Indeed – having read so many chapters of the textbook on cancer biology, I was FAR better equipped to understand what I was hearing – and many of the research topics presented picked up exactly where the textbook left off. I also have a pretty good idea what questions they will be asking now: I can see where the questions during my committee meetings have come from; it’s never far from the research they’re most interested in. Finally, the big picture is coming together!
Anyhow, two specific things this week have stood out enough that I wanted to mention them here.
The first was the keynote speaker’s talk on Thursday. Dr. Morag Park spoke about the environment of tumours, and how it has a major impact on the prognosis of the cancer patient. One thing that wasn’t settled was why the environment is responding to the tumour at all. Is the reaction of the environment dictated by the tumour, making this just another element of the cancer biology, or does the environment have it’s own mechanism to detect growths, which is different in each person. This is definitely an area I hadn’t put much thought into until seeing Dr. Park speak. (She was a very good speaker, I might add.)
The second item was something that came out of the textbook. They have a single paragraph at the end of chapter 12, which was bothering me. After discussing cancer stem cells, DNA damage and repair, and the whole works (500 pages of cancer research into the book…), they mention progeria. In progeria, children age dramatically quickly, such that a 12-14 year old has roughly the appearance of an 80-90 year old. It’s a devastating disease. However, the textbook mentions it in the context of DNA damage, suggesting that the progression of this disease may be caused by general DNA damage sustained by the majority of cells in the body over the short course of the life of a progeria patient. This leaves me of two minds: 1), the DNA damage to the somatic cells of a patient would cause them to lose tissues more rapidly, which would have to be regenerated more quickly, causing more rapid degradation of tissues – shortening telomeres would take care of that. This could be cause a more rapid aging process. However, 2) the textbook just finished describing how stem cells and rapidly reproducing progenitor cells are dramatically more sensitive to DNA damage, which are the precursors involved in tissue repair. Wouldn’t it be more likely then that people suffering with this disease are actually drawing down their supply of stem cells more quickly than people without DNA repair defects? All of their tissues may also suffer more rapid degradation than normal, but it’s the stem cells which are clearly required for long term tissue maintenance. An interesting experiment could be done on these patients requiring no more than a few milliliters of blood – has their CD34+ ratio of cells dropped compared to non-sufferers of the disease? Alas, that’s well outside of what I can do in the next couple of years, so I hope someone else gives this a whirl.
Anyhow, just some random thoughs. 6 days left till the exam!