Thursday, March 31, 2011

The biology of memory - what do YOU have to say about it for 1000€?

Literature and arts get close to science for the third consecutive year with the Ellipse Award organised by the Barcelona Biomedical Research Park (PRBB).

This award started three years ago by initiative of a group of young researchers of the park, and it is aimed at anyone interested in biomedical research - whatever their training and profession. It gives them the opportunity to explain a particular concept related to biomedicine using, amongst other genres, a fictional story, a poem, an essay, a theatrical script or any form of graphical work.

In the spirit of reaching as many people as possible, the texts can be written in Catalan, Spanish or English.

Under the Alzheimer International 2011 initiative, the prize this year will be awarded to the best works that address any aspect related to the biology of memory from a scientific perspective (e.g. the biochemistry of memory, its physiological conditions, the diseases that cause its alteration or the potential treatments to restore it).

The prize is 1000 Euros for the winning entry in each category: graphics and written, and the deadline for sending your work is July 15, 2011. For more information:

Good luck!!

Monday, March 28, 2011

Cis-regulation and genome architecture during development, evolution and genetic diseases

That's the title of today's PRBB-CRG conference by José Luís Gómez-Skamerta. I learned many things, but here’s two interesting ones:

1-3C (Chromosome Conformation Capture), a high-throughput molecular biology technique used to analyze the organization of chromosomes in a cell. In particular, it allows one to check whether two very distant DNA regions interact with each other via cross-linking, digestion and re-ligation. I had heard about it before, but had forgotten, and it’s quite cool, isn´t it?

2-How the 3D structure of the genome (and particularly, the formation of loops on the DNA) can add a new level of complexity to gene regulation. Gómez-Skamerta showed us how the same collection of genes and the same collection of enhancers can have a very different result through evolution (in different organisms) and through development (at different stages), and one way of achieving this is via the DNA loops. How? Using the example of the Iroquois genes (Irx), which he originally cloned, he showed how keeping two promoters (and several enhancers) within one same loop facilitated the fact that these two genes are activated by the same enhancers. It also explains why those enhancers in the loop have more difficulty to activate a gene outside the loop.

And that’s my very brief summary :)

Friday, March 18, 2011

Evolutionary medicine - understanding malaria drug resistance

Forgetting for a minute their use of complicated mathematical formulae, scientists are, really, like children. They ask: why? And when they have the answer, ask again: but why? And once a satisfactory explanation has been found they wonder, but why? And on and on and on…

But this stubbornness pays off. Daniel Hartl, from Harvard University, gave us an example today of how this relentless questioning actually helps come up with interesting and useful explanations about how things are the way they are.

In his talk at the PRBB Conference Hal, Hartl talked about the evolution of drug resistance in the malaria parasite. He pointed out how the different existing treatments for malaria that have existed have been effective for less and less years each, before resistance appeared.

He focused on his analysis of DHFR, a parasite enzyme which is the target of the antimalaria drug pyrimethamine. There are 4 aa changes that can be combined following 24 potential evolutionary pathways. Hartls simulations and laboratory experiments (using E.coli) showed that only three of those account for most of the outcomes. When he checked the ‘real world’ and looked at all the polymorphisms that exist for DhFR he found that, indeed, there were few that were common, and these coincided with those he found to be more successful in the lab.

Now come the questions :)

Hartl found that a particular polymorphism very common in South East Asia (which contained all four aa changes, let’s call it 1111) was not present in Africa. Why?, he asked (especially since he found some resistant strains found in Africa had their origin in East Asia). Well, he found that the fourth mutation had a high fitness cost associated (the enzyme was less efficient), so it was not very good. ..

But then (second why) why was that mutation present in Asia to begin with? Well, because in Asia those 1111 strains had high copy numbers of a gene linked to the 1111allele which coded for the enzyme substrate, and those high copies resulted in high levels of the enzyme substrate, which meant that having a less efficient enzyme was not that bad.

But then (yes, a third one!) why was that CNV not present in Africa? Well, it turns out that while in Asia people are usually only bitten once, in Africa a person can be infected by several parasites at the same time. That means that recombination takes place between the different parasites, and therefore the CNV and the 1111 allele are easily separated. Therefore, having a 1111 is bad, and it’s not compensated by high copy numbers of the CNV, because they are not linked.

Interesting, eh? If you (or your 3-year old child) can think of any other whys don’t be shy, contact Daniel Hartl who, I am sure, will be delighted to keep on investigating…

Wednesday, March 2, 2011

Of sex and death

Why does sex exist? And why having sex with another organism instead of oneself? These are two of the questions that Patrick Phillips, from the Unviersity of Oregon, tried to answer in his talk at the PRBB last week.

The biologist uses the nematode C.elegans for his research, which consists primarily in recreating evolution in the lab. How does that work? It basically consists of two steps: artificial selection+adaptation to the laboratory conditions. That is, he creates a novel environment, generates mutations in the worms, and sees which ones adapt and which ones die. Cruel? Not more than reality…

The advantages of these evolutionary experiments in the lab is that they are controlled and can be replicated. The problems are that they are limited in time (while real evolution takes 1000s of years) and there’s also a limited population size, which means that rare events (as in rare mutations) won’t be seen. Regardless of these inconveniences, Phillips managed to convince the audience that these experiments can prove that sex is good – to get rid of deleterious mutations and to increase genetic variation, which provides a better adaptation to the changing environment.

According to the scientist, one reason C. elegans is good for studying evolution is that they can be frozen. When you are doing the kind of experiments he does, if you freeze worms from different generations along the experiment, you have the equivalent to a ‘fossil register’ that allows you to compare the organisms at the ‘beginning’ and the ‘end’ of the evolution phase you are studying. Isn´t that cool?

Apart from sex, Phillips also talked about death – or why we age. Again, the elegans nematode plays an important role in ageing research: actually some mutants can live up to 10 times their usual lifespan. That is the equivalent of a human living 1000 years!

His experiment consisted in breading the worms for 323 generations by selecting only one worm in each generation to spread the population. As a consequence, the population size went dooooown and the worms were very sick (ah, the lack of genetic variation!). He then, playing God, saved the species by letting a higher number of worms reproduce for another 60 generations. When he compared the genome of the sick (thanks to his ‘fossil record’) and the recovered worms he found very few changes: only about 10 nucleotides! He went back in history to check when each change had taken place – again, thanks to the frozen worms (amazing, eh?). What he found is that the ‘recovery’ mutations were not the result of ‘mutating back’ to the original sequence, but rather they were compensatory mutations.

All in all, he showed us what he called an ‘emerging paradigm in evolutionary biology’, a new way of studying evolution: create a perturbation (mutation); propagate the species for 50-100 generations to let them recover fitness; sequence the genome to find out which changes have occurred; use genetics to confirm the results.

Voilà! Now you can try it at home :)