Highlights from Dr Elizabeth Blackmore’s talk on telomeres and telomerase

Unfortunately because this is a quick post I don’t have time to locate references for some of the things I learned tonight:

• Telomerase levels, and telomere length, are very strongly correlated with a gamut of human health outcomes, from stress to heart rate to longevity to abstract psychometrics like ‘rumination’.
• Telomerase resembles a kind of reverse transcriptase with a built in fragment of RNA that acts both as a kind of primer for the target telomere and as a functional moiety.
• Longevity has a far greater inherited component that I knew, but this only seems to kick in over the age of 75. Past that age, higher telomerase levels and longer telomeres have a strong negative correlation with geriatric diseases such as cancer and cardiovascular disease.
• Telomerase isn’t just good for extending telomeres. Even if RNA interference is used to disrupt the RNA portion of the enzyme, making it impossible for it to bind to DNA, telomerase levels have strong phenotypic correlates. In one experiment, induced higher telomerase levels lead to stem cell proliferation – the mouse model became a ball of fur because it had such a high density of new follicular cells.

Overall the talk was a perfect balance of hard science and human interest. Dr Blackmore is an excellent speaker and I strongly recommend seeing one of her presentations if you have the chance.

Scientists characterise active region of telomerase

From ScienceDaily:

“Telomerase is an ideal target for chemotherapy because it is active in almost all human tumors, but inactive in most normal cells,” Skordalakes says. “That means a drug that deactivates telomerase would likely work against all cancers, with few side effects.”

Not to mention the potential for longevity treatment, and of course the inevitable skin lotions. I don’t know much about human (or eukaryotic for that matter) cell biology so I’ll leave any more commentary to the experts. The Royal Society of NSW is hosting a public lecture in Sydney tomorrow night on “Roles of Telomeres and Telomerase in Human Health and Disease”. The speaker is none other than Dr Elizabeth Blackburn, co-discoverer of telomerase. Glancing at her wiki entry, I found that she was also kicked off the President’s Council on Bioethics for trying to inject some actual science into their recommendations.  Win.

Tip: PCR when your target has strong secondary structure using DMSO and Q-solution

This post falls into the category of “things I couldn’t find myself online, so I’m posting for the sake of others with the same problem”. While there are a few articles and pages scattered around offering advice on PCR additives, the following excellent tips came from a random old faculty dude in my school:

• The best PCR additives for improving your chances of amplifying a target with strong secondary structure (including RT-PCR of folded RNAs, which is my big problem at the moment) are Dimethyl sulfoxide (DMSO) and Qiagen’s Q-solution.
• While a lot of websites will tell you to use DMSO at about 5-10% (of your final reaction mix, not the master mix), it can actually be brought up to about 30%. If you’re not getting results at a lower conc., try ramping it up.
• It’s crucial to use pure DMSO. It’s fairly cheap stuff so order some in if you are unsure.
• Although it is possible that DMSO will be slightly mutagenic, it’s really nothing to worry about unless you are going to be re-amplifying something multiple times, in which case you should be worrying about other sources of mutagenesis anyway.
• Q-solution is probably just betaine. While it’s true that you can buy raw betaine cheaper than Q-solution, if your lab is anything like mine there are probably a million tubes of Q-solution lying around in old, abandoned kits and hence it is probably the cheapest and most readily available additive. Use it at a final conc. of about 1M.

DISCLAIMER: I am but a humble research student and definitely not a master of PCR. I’m simply repeating advice that I found useful. This advice is given as-is and I take no responsibility for failed PCRs, nervous breakdowns or raidings of the lab next door’s chemicals cupboard.

Just a little poke…

Towards the end of a fascinating talk by MIT’s Drew Endy a member of the audience made a sweeping statement about the economics of vaccine research. The gist of the comment – with which Endy casually agreed – was that there was no incentive for Big Pharma to put R&D money into a highly effective influenza vaccine which would erode its own market when they can continue to make semi-effective vaccines for whatever serotypes happen to pop up each year, guaranteeing an annual return.

I’ve heard many variations on this argument before, and am still gobsmacked that anyone finds it even remotely plausible. Why is the vaccine industry always the target of this sloppy reasoning? Do the same people believe that, if unregulated, surgeons would only perform only partial tumor removals so as not to erode the cancer treatment market? Ethical issues aside, no surgeon in their right mind would pass over the incredible profit opportunity to offer cures when their competitors are offering only treatments.

In fact, the existence of partial vaccines such as influenza increases the profit potential of a full vaccine. Think of the institutional pressures that would be put on, say, a vaccine that acts as a complete prophylaxis against cancer. There is nothing like it on the market; outside the suicidal and extremely old, there are few people for whom it would not be a hugely valuable and non-substitutable good. Biomedical products take years and billions of dollars in capital to develop, however, and even with tremendous demand and economies of scale there would be a sizable group of people who could not afford it. Populist governments being as unpredictable as they are, this is a very risky investment for any Big Pharma: will they face broken patents, price controls, boycotts, or more?

Counterintuitively, producing a vaccine for a more mature market would provide a much safer return on investment. Few people would be outraged if only the elite can afford the immune-for-life influenza shot, as long as the elderly and sick can at least get their yearly boosters.