OYM28: Untangling HSPs Genetic Network 1

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Circles of Life 2013 (c) Martin Krzywinski

Circles of Life 2013 (c) Martin Krzywinski

This week on the On Your Mind Neuroscience Podcast:

It’s amazing how much a disrupted schedule can affect productivity.  This week, Liam and Kat have had their sleep patterns turned upside down for one reason or another and are dealing with the repercussions.  In Liam’s case that means working in the lab until the early hours of the morning and for Kat, it means accidentally locking herself out of her apartment for hours on end.  On the other hand, Adel’s joining us remotely again, because he’s dealing with some of the banking bureaucracy for his move to med school.

But on a more positive note, the gang’s been working on the début On Your Mind poster presentation, showcasing the awesomeness of podcasting at the Interdisciplinary Graduate Student Research Symposium here at McGill.  If you’re in the area and want to check out the conference, meet us in person or score a sweet OYM business card, then drop by!  It’s April 1 and 2 at Thompson House on the McGill campus.

This week’s episode starts with some borderline sci-fi science that Liam’s come across.  It’s a paper, published in NeuroImage that is able to, eerily, recreate a photo that a person’s looking at by modelling the activation of a number of cortical areas.  It uses a precise fMRI paradigm to generate “neural portraits of perception” in a way that hasn’t been achieved by traditional methods of translating visual processing.

Along the same line, Kat’s read a report that scientists are “successfully reversing aging” and that human trials are imminent.  After a bit more investigation into the Cell paper that was referenced in the article, it looks like scientists have described biochemical pathways that become less tightly regulated with age and, by supplementing aged mice with some of the missing factors, they can revert the effects of aging in specific tissues.  While it’s still very interesting science, it sends us into a discussion about the need (or not) of a treatment for aging.

This week’s paper, in Science, reports on a tremendous amount of work identifying, validating and interpreting genetic variants associated with a neurodegenerative disorder.  Hereditary spastic paraplegias (HSPs) are a group of common, but often complex disorders that are characterized by the degeneration of axons in the corticospinal motor tract.  As their name suggests, they can be caused by a number of genetic mutations with varied modes of inheritance.  In this study, the authors focus on patients with an autosomal recessive form of the disorder and their families to perform whole exome sequencing.  This technique sequences only the coding regions of genes, as these are the areas of the genome with the highest likelihood to impact protein functioning.  The authors identify mutations in genes known to be associated with HSP as well as in 15 new genes.

Next, the authors used zebrafish to investigate the potential impact of their mutations on development and functioning.  By mutating, and decreasing the expression of the zebrafish ortholog of their candidate genes, they determined that many of them were crucial to survival or necessary for normal motor behavior.

When the 15 candidate HSP genes were added to known HSP “seed” genes, their interactions were mapped to create, what the authors call, the HSPome: the network of proteins and interactions involved in the disorder.  Using network analysis tools, they determined that the nodes of their HSPome were significantly associated with each other, and more closely related to the networks of other neurodegenerative disorders than to more general neurological gene networks.

This may be one of the most convincing gene network papers that the three of us have seen in a while.  It’s thorough, well supported and well written, but its title only earns part marks on our title test, for being less than informative.

This Weeks Paper:

Novarino G, Fenstermaker AG, Zaki MS, Hofree M, …, Ideker T, & Gleeson JG (2014). Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science (New York, N.Y.), 343 (6170), 506-11 PMID: 24482476

(and a sneaky PDF for those without access)

THE LINKS:

Mitochondrial dysfunction in aging (PDF):  and a Guardian article that blows it out of proportion:

Reconstructing face images from evoked brain activity 

The Case for Beautiful Science by  Johanna Kieniewicz

For even more pretty (but detestably comprehensible) big data check out the Wired article by Brandon Keim

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