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The little fish with big potential

I had the opportunity to chat (over a beer, of course) with Dr. Bryan Crawford last week about his research in the UNB biology department. He’s the recent recipient of the Faculty of Science Excellence in Teaching Award and manages a remarkable zebrafish-rearing facility in the C.W. Argue Research Wing of Bailey Hall. His research is innovative and his passion for it seeps into every conversation he has.

Dr. Crawford strives to understand the link between genotype (the information in your DNA) and phenotype (the physical manifestation of that information – the patterns in your cells and body). Living cells contain a complete set of DNA, yet those cells somehow decide which parts of your DNA they will choose to use. For example, your brain cells contain the genes for making muscle proteins, but choose not to – instead, they use only the skin-related genes.

There are complicated and unknown control mechanisms that help cells decide which genes to use, communicate with one another about those genes, and organize themselves into complicated tissues like muscle, toenails, taste buds etc. The cells of these tissues produce a matrix of different substances in order to hold the tissue together (so that you’re not a “pile of goo on the floor”) and give the tissue specific properties (elasticity, strength, malleability, etc.). Dr. Crawford’s research specifically investigates how cells choose where to create this matrix and when to remodel it into another form, using molecules call matrix metalloproteinases (or MMPs). So how do zebrafish help him investigate those control mechanisms?

Zebrafish (Danio rerio) are a species of Southeast Asian freshwater fish about the size of a house key. They’ve become a popular aquarium fish worldwide, with many different colourful and interesting strains. They’re also gaining popularity in biological research since they’re considered a near-perfect “model organism” (some other model organisms include white mice and fruit flies); it only takes three days for them to hatch after eggs are fertilized, they’re raised in freshwater (so we don’t have to pump ocean water into the lab), they’re vertebrates (just like us), and their embryos are completely transparent. Furthermore, we’ve sequenced their genome, so we know what genes are in their DNA.

This has allowed researchers worldwide to create different genetic strains – certain genes can be added, removed or inhibited, depending on what questions you’d like to answer. For example, there are completely transparent zebrafish strains with fluorescent proteins attached to their blood cells, so that their blood lights up under certain conditions and their circulatory systems can be observed.

Given that these fish can be cultured quickly and their genome can be manipulated (relatively) easily, it seems obvious why Dr. Crawford uses them in his lab. They have a very similar matrix holding their cells together as us and their MMPs can be manipulated to remodel the matrix in different ways.

Dr. Crawford’s graduate students are currently working on a variety of different questions about this matrix and the associated MMPs. For example, Emma Chaston-Vickers has developed a method to visualize the activation of MMPs and will be using it to determine how MMP activity is regulated during development. Emma Matchett is currently trying to tease apart how active MMPs interact with inhibitors once they begin remodelling the matrix.

Knowing how MMPs are supposed to function and how they are inhibited is important information, since these remodelling molecules can sometimes get out of control – particularly when tumours are spreading through different tissues. If we can tell when our MMPs are out of control (in diseases like cancer and arthritis, and during heart attacks) and how they would normally be stopped, we might have a better chance at preventing the damage they can cause.

If Dr. Crawford’s lab is able to address this many challenging questions about the matrix between our cells, just think of the other questions we could address with zebrafish! Questions about cells, organs, organ systems, behaviours, disease, pathogens, nutrition and food production – to name a few. If I could pack that much potential into my house key, I would have already been to the Moon a few times, solved world hunger and stopped forgetting my keys everywhere…

For more information about the wonderful world of zebrafish, head to http://zfin.org.

I’ll be on hiatus over the holidays, but you can look forward to learning more about fish in January’s column! Good luck with final exams, and remember – stay curious.

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