Thursday, January 29, 2009

Genome Canada cut from the budget?

So at a time where our southern neighbors are investing heavily in science and putting science back into decision-making we have an unpopular prime-minister (at least out east), who is crippling science and rendering us completely uncompetitive. The latest casualty is Genome Canada, our only large-project funding agency, completely left out of the budget. I hear a lot of grumbling, and it's only a matter of time before we experience major brain-drain. Such a reversal in a short amount of time. From the Globe and Mail:

The only agency that regularly finances large-scale science in Canada was shut out of Tuesday's federal budget, putting at risk thousands of jobs and some of the most promising medical research, and forcing the country to pull out of key international projects.

For the first time in nine years, Genome Canada, a non-profit non-governmental funding organization, was not mentioned in the federal budget and saw its annual cash injection from Ottawa - $140-million last year - disappear.

"We got nothing, nothing, and we don't know why," said a stunned Martin Godbout, Genome Canada president and CEO. "We're devastated."

The news spread like a virus through the research community yesterday as the country's top scientists wondered whether the oversight was a mistake. Genome Canada supports 33 major research projects in areas such as genomics, agriculture and cancer stem cells with operating grants of $10-million a year. The projects employ more than 2,000 people. By comparison, medical research grants from the federally funded Canadian Institutes of Health Research run in the $100,000-a-year range.


Wednesday, January 28, 2009

Science and the 2009 Canadian Budget

Looks like the granting agencies took a hit with the Canadian Conservative Governments new budget.
From the Globe:
The headline numbers offered yesterday drew praise from university leaders. There is $2-billion for colleges and universities to fix their aging buildings, $87.5-million for new graduate scholarships and $750-million for the Canada Foundation for Innovation, which funds research infrastructure.

But more than 250 pages back in the budget are figures that point to cuts to the three federal granting councils, the bodies that hand out the money to support continuing research. Over three years, the base budgets of the three agencies will be reduced by $87.2-million; the government says this money will be directed to other spending programs in higher education.

At a time when U.S. President Barack Obama has pledged to "restore science to its rightful place" with billions in new investments, leaders in the Canadian research community were left scratching their heads over Stephen Harper's response to what many fear will become a widening funding gap.

Also it sounds as if environmental investments are exclusively carbon capture and storage. Also the money given to the auto sector had less green strings attached than what was done in the US.

Yet, the budget was mostly silent on the science sector, other than for infrastructure investment in universities and colleges, while its commitment to the energy sector, particularly when it comes to green projects, seems limited to carbon sequestration efforts to which it has already committed, and a green infrastructure fund to transmit power from renewable energy projects. Research and development in this area got scant attention.

Overall doesn't sound very competitive with what the US has decided to do to take on this 'financial crisis'. I was optimistic that the Conservatives might have done something smart, because I have no doubt they have some smart people, especially since they have to please the opposition. Lost opportunity.

"catching fish and chopping wood, the revolution, slow time coming" Buck 65


Tuesday, January 27, 2009

Posts and Hosts

Charles at Science and Reason has volunteered to host the upcoming 18th edition of the Cancer Research Blog Carnival to appear on Feb. 6. He currently has a bunch of cancer posts up himself, but be sure to submit your own posts for the carnival here.

We also need hosts for March and onward. Email us to sign up!


Friday, January 23, 2009

Move over GFP, it's FlAsH and ReAsH

Just read a paper that follows a viral protein in live cells using the smallest fluorescent tag available. In this paper they follow a protein that could not previously be labelled with a GFP tag. While extremely useful for many applications as a fluorescent tag to follow protein localization, GFP can disrupt the function of some proteins, thus defeating the purpose of labelling it in the first place. This recent paper makes use of a technology I had previously not heard of; biarsenical labelling of tetracysteine motifs. Tetracysteine motifs are exceedingly small, only six amino acids, and are therefore much less likely to disrupt protein function, however, they are still useful for affinity purification of your labelled protein. These amino acids then interact, non-covalently, with a biarsenical molecule which then greatly increases fluorescence of the molecule. Apparently this was originally found in 1998, and I just heard about it now. Invitrogen, a former sponser of the Bayblab (perhaps they don't approve of animal penises), sells the technology and, I presume, owns it aswell. The invitrogen website has a reasonable explanation of the commercially available system as well as links to the original references. Additionally there are some supplementary figures with movies using tetracysteine labelling technology, nothing extremely impressive or free access however.


Wednesday, January 21, 2009

Turning Stem Cells Into Cancer

An interesting new paper (Open Access, click away!!!) exploring the cancer stem cell hypothesis, describing to my knowledge the first transgenic cancer model to be derived by specifically targeting a normal stem cell population. The Spanish group of Maria Perez-Caro et al. show that they can induce chronic myeloid leukemia (CML) in mice by introducing the infamous bcr-abl oncogene (a gene encoding an aberrent fusion protein known to drive the human disease), specifically into Sca1+ normal hematopoietic stem cells.

They go on to use the model to investigate an important corollary of the cancer stem cell hypothesis, which postulates that residual CSCs are responsible for disease remission during/following therapy. They show that their CML mice cannot be cured with the bcr-abl targeted inhibitor STI571/Gleevec, whereas ablation of the Sca1+ stem cell compartment is sufficient to eliminate the disease. Therapeutically speaking they cheated a bit here by simply engineering a suicide gene into the oncogene cassette, but it's a start. It would be nice to see whether a therapeutically relevant approach to CSC depletion (ie anti-Sca-1 MAb) would also be able to eliminate the disease in their model.


siRNA cream for STDs

There is a small pharma company that is touting a new anti-herpes cream that protects against HSV-2 transmission. The cream contains two siRNAs: one targeted at nectin in the cells of the vaginal lining and the other UL29 in the viral genome. Nectin ko mice are resistant to HSV infection and UL29 is presumably vital for the virulence. The delivery is via a lipid system. Obviously this would be a nice approach to a number of viral STDs including AIDS. However I couldn't help but facepalm when I read the press release:

"As a new route to making better drugs, several companies have locked onto technology using small, interfering RNAs or siRNAs. These are molecules that can silence microRNAs -- tiny strands of RNA, or ribonucleic acid, that help turn genes into proteins."

Really... really?

But it makes we wonder, how long before we have an miRNA cream? They are, after all, bigger than siRNAs. Even bigger than p53.


Tuesday, January 20, 2009

Odds of finding life on Mars

When I first read about the "Big Belch" on Mars, in the Sun of all places, I was a tad incredulous. Turns out however that the evidence is pretty tantalizing. But short of going there and digging we won't know for sure. What do you think are the odds that the origin of the methane is biotic? Turns out bookies have stopped taking bets since the discovery. In the 1970's the odds of finding past or present life on Mars were 1000:1, and before the discovery they were hovering around 16:1. Bookies however are still taking bets on whether life is still present on Mars at 500:1 (seems like a good bet to me), and whether president Obama will announce the discovery of intelligent extra-terrestrial life in this current year, and the odds are 66:1 (seems like a bad bet to me). Gentlemen, time to make your bets, comment with your odds and the wisdom of the crowd will enlighten us.


Incentive to graduate

I'm often accused of being a career student. A decade studying at a university is not nearly as bad as it sounds, but it's enough for me... This guy however never stopped, accumulating 27 college degrees, including 19 masters and one doctorate. I guess he just collects them. Time to finish up my ph.D. before I too turn 67.


Sunday, January 18, 2009

Debts Real and Percieved

Simultaneously one of most insightful and hilarious things I've heard in a long time. In her 2008 Massey Lecture, Margaret Atwood explores the nature of debt through the modern-day tale of "Scrooge Nouveau". Proving that with a little imagination, it's possible to derive inspiration and humor from something as depressing as the economic realities of our times. This is why we need writers.

You can listen the 2008 Massey Lecture podcast "Payback: Debt and the Shadow Side of Wealth" here, courtesy of public broadcaster TV Ontario. If you enjoy this sort if thing it's also worth poking around the TVO website, and subscribing to the Big Ideas podcast in particular. They usually have great stuff.


Saturday, January 17, 2009

Mess With Your Head

I'm sure many of you have tried the old trick of standing in a door frame, pushing your hands out against the sides then stepping out and having them 'magically' rise. The Boston Globe has an article describing some other mind tricks - including drug-free hallucination. Check it out and try them out.

[h/t: Culture Dish]


Wednesday, January 14, 2009

Cloning Perfection

10/10 positive clones. Not the first time, but each is just as sweet as the last. And a sexy gel to boot. What can I say? When you're hot, you're hot.


Tuesday, January 13, 2009

Cheap Minipreps Now!!!!

Here in the Bay we purify a heck of a lot of plasmid DNA using over-priced commercial kits. Mainly because there's a fully stocked Qiagen biobar down the hall and this set-up appeals to our excessive laziness. But sometimes even laziness can have its limits. Maybe the Ottawa transit strikes and blizzards are getting to me. Whatever the reason, today I was particularly struck by the ridiculousness of shelling out hundreds of dollars of grant money for a week's supply of aqueous solutions and mass-produced plastic tubes, packaged in totally unnecessary cardboard and throwaway Nalgene bottles. Surely a Ph.D. biochemist can come up with something more efficient than this?

The simple two-step procedure used by Qiagen and most other commercial plasmid prep kits is no secret. First comes Birnboim's alkaline lysis - a series of three buffers that lyse the bacteria and then neutralize the lysis reaction. Second, plasmid DNA is purified from the lysate by passing it over a silica column in the presence of high salt. Making the buffers is trivial (see below). Plus, we probably have a lifetime's supply of unused buffers from previous Qiagen kits lying around the lab. So we're paying for the little plastic columns. About $1.60 CAD a pop. Making the columns is probably not much fun, and alternative materials don't seem to be as efficient. But in theory there's no reason the columns can't be re-used.

The idea of regenerating commercial miniprep columns first came to my attention a while back. This paper/ad described a two-buffer product called MaxxBond that allowed columns to be regenerated and re-used up to ten times. I liked the idea of recycling columns, but not the idea of relying on yet another over-priced, proprietary/patented technology of an unknown nature. I was particularly concerned about the possibility of unknowingly cross-contaminating my plasmid preps, which would be a total nightmare. It's impossible to assess the risk of this happening without knowing how the columns were being regenerated.

After a little discussion in the Bay today, a quick surf on the Google produced a better alternative now floating around the interweb. The Indian research group of Ranga describe a method that involves simply storing the columns in hydrochloric acid and rinsing them with water when you're ready to use them again. They claim commercial columns can be re-used 10-20 times in this way. What I find appealing about this method is that the HCl acid works by physically destroying residual nucleic acid from your last prep, so it would seem pretty much impossible to cross-contaminate the next one. And a 10-fold increase in column productivity sounds pretty darn nice, and drops that price from $1.60 to 16 cents per prep. I think I might actually try it.

The protocol is available here, and more info can be found in a paper here.


Friday, January 09, 2009

Evaporation Rates of Ethanol Solutions

A few years ago, a crazy post-doc posted the following sign at the bacterial bench:

"Do not use 70% ethanol to sterilize the wand, it does not burn completely. Better yet, 70% becomes 50%, becomes 30%... WATER DOESN'T BURN!!"
More recently in a comment, Kevin Z muses, "I don't really see how it matters to make fresh ethanol dilution or keep a 85% stock around." Being graduate students, and having totally forgotten basic high school science, this became a question: Is this true, does ethanol in solution evaporate preferentially over time? (Of course, being graduate students, it took 2 years to come up with and test the question).

There were two schools of thought on the possible answer:
1) A mixture of water and ethanol will form a perfect solution with its own unique properties (different percentages will have different evaporation rates but the ethanol percentage will remain constant over time)
2) Ethanol, being more volatile than water, will preferentially leave solution resulting in a decrease in ethanol content over time.

To answer the question, a series of ethanol dilutions ranging from 0 to 100% were prepared and left open on the benchtop in 15 mL tubes (10mL of each dilution). The volume was recorded every day for a period of 1 week and plotted.

Figure 1: Change in volume of open ethanol solutions over a period of 1 week. Slopes represent evaporation rate (mL/hour).

As Figure 1 demonstrates, each solution has a unique evaporation rate and slopes appear roughly linear. However, closer examination reveals that the graphs are not linear but rather the slope of each curve changes subtly over time. That is, for example, the calculated slope of the line over the first 3 days differs from that over the last 3 days (data not shown). This change in evaporation rate over time suggests that the ethanol content of each solution is changing, in line with view (2).

Because the changes in slope were subtle, a second metric was chosen to verify that the ethanol content of each solution was changing over time. For this, the mass of one mL of each solution was measured at the end of the week and compared to the density of solutions of known composition.

Figure 2: Density of various ethanol solutions. Diamonds indicate the density of freshly prepared solutions at the indicated ethanol percentages. Bars indicate the measured density after one week on the benchtop.

As can be seen in Figure 2, the density of ethanol solutions does, in fact, change over time - indicated by the difference between the points and the height of each bar. The difference is most noticeable at mid-range mixtures (~30 - 50% EtOH). Final ethanol percentages after one week were calculated based on the known standards. (I realize the x-axis doesn't scale correctly [eg. the space between 0 and 10 is the same as between 10 and 30], this was a quirk of Excel that I couldn't figure out in a short amount of time. The standard curve and R2 were determined on a separate graph with proper scaling [not shown] using the same data) The summary can be seen in the table below.

Table 1: Summary of Ethanol Densities
% EtOH in solutionDensity (g/mL)Density (after 1 week)Estimated final % EtOH

Long story short, the postdoc in question was correct. After a week on the bench, 70% ethanol used to sterilize bacteria spreading wands will be a shadow of its former self. Regarding Kevin Z's comment, if you're in the habit of leaving 85% EtOH open on the bench, then by all means you should be making it fresh - but I suspect that's not the case. This carries over to other areas in the lab as well. Oft times, the people filling TC spray bottles with 70% ethanol for sterilizing work surfaces (maybe this is where the confusion at the bacterial bench comes from?) will prepare too much and leave the excess in a graduated cylindar on the bench - sometimes covered, sometimes not - to fill bottles at a later time. This, again, will lead to evaporation of ethanol and spray bottles filled with less than 70%.

This could have been figured out in a much simpler way. Water and ethanol form an azeotrope - a mixture whose composition can't be changed by distillation - at a ratio of 95.6 : 4.4 ethanol : water. In this mixture, the vapour has the same constituent ratio as the solution. Other ratios will have one component evaporating off at a different rate than the other. Which is why, of course, we're able to distill spirits to increase their alcohol content. Check out the above link to read more about azeotropes, phase diagrams and Raoult's Law.

The real lesson, though, is to put the cap back on your Jameson's when you're not drinking it.


Thursday, January 08, 2009

Come into my parlour...

...said the spider to the




Sunday, January 04, 2009

Bayblab Makes the Grade

A Blog Around the Clock has just announced the winners of The Open Laboratory 2008. The Open Laboratory is an annual anthology (now in its third year) of "the best science writing on blogs". This year's collection consists of 50 posts from around the blogosphere - whittled down from over 500 nominations - plus science-themed comics and poetry, and a post from the Bayblab made the cut. We join the illustrious company of heavyweight blogs like Bad Astronomy and The Loom as well as several other top notch science blogs.

Check out the full list of posts here.

The book itself will be available soon from in both print and digital versions.


Saturday, January 03, 2009

Health Carnival Combined Feeds

If you're a regular reader of the Cancer Research Blog Carnival, chances are you read some of the other great health and medical carnivals out there. If that's the case, here's a little post holiday treat for you: Walter from HighlightHEALTH has set up RSS feeds for several blog carnivals, including our own Cancer Research, as well as a combined feed for all of them.

What's the difference between these new feeds and existing ones (such as the feed for the Cancer Carnival homepage)? Well, instead of calls for posts and announcements (like this one), each feed is just for the published editions of the respective carnivals.

The included carnivals and their individual and combined feeds:
Combined feed - one subscription, all eight carnivals

Individual Carnivals:
Grand Rounds
Change of Shift
Medicine 2.0
Gene Genie
Cancer Research
Health Wonk Review


Friday, January 02, 2009

CRBC #17

The latest edition of the Cancer Research Blog Carnival, and first of the new year, is up at Blind.Scientist. It's chock full of good stuff, so go check it out. Then send us an email to host the next one.