Murray Blackmore

Starts with a picture of his mom, who looks like a sweet, ordinary grandma — except she’s been living with a cervical injury for 25 years.  He gets it.  He thinks this event is humbling.

Why can’t axons regenerate?  The cord is hostile to axon growth . . . and because neurons are limited in their ability to respond.  Neurons have a built-in no-growth policy.  He’s been looking at this for his whole career.

Why not?  Why can’t axons do what they do in fish and flies and human newborns and in human peripheral nerves?

Oh good, gene expression mini-lecture.

If you start with an embryonic neuron, the axon will grow, but later not.  If it has to do with DNA, and all our cells have the same DNA, why don’t they behave the same way at different times?  Because at different times, the genes that make up the DNA are variably active.  DNA gets transcribed into RNA, and RNA builds protein . . . it’s the kind of protein you have that determines what the cell does.

So how does this change?  Between the DNA and RNA are transcription factors.  If you want an old neuron to behave like a very young one, you need to get your head around that transcription process.  You look at the genes that are expressed differently in “old” neurons . . . and you target them to knock them out.  You also look at the genes that are expressed in only the very “young” ones and try to restore them.  (Old and young here refers to human developmental stages, not chronological years since birth.  A young neuron is under construction in the developing embryo.  And old one belongs to a newborn baby.)

Arlotta et al 2005 had done this work . . . there are more than 1,000 genes that change between young and old.  Ugh, needle in a haystack.  At the Miami Project, a couple of researchers came up with a method to sort them out . . Unbiased Phenotypic Screening–aka, “Let’s ask the neurons.”

Step 1.  get the DNA that encodes the genes, which is easily done.

Step 2.  deliver the DNA to neurons in culture, which is not hard to do, unless you’re doing it on a large scale.  They can test 96 different kinds of DNA in a single experiment.

Step 3.  use automated microscopy to measure axon growth, which is done with computer algorithms.  You get back enormous data files, 10s of 1000s of individual cells per experiment, and you can see them one at a time, which exact genes make axons longer.

That’s where his postdoc ended. (Jeebus.)

So, can you use this info to manipulate those genes into their young, axon-growing state in order to get recovery?

A gene is just a stretch of DNA, and you can use a virus to deliver whatever transcription factor you want to your DNA . . . they’ve set up a rapid testing of candidate genes in a rodent sci model.  They put the virus in, do a cervical hemisection, and then, 8 weeks later, sacrifice the animal and do the analysis.  They found one transcription factor that succeeded in persuading the targeted gene that it was young . . . and as expected, it made axons grow past the injury site.

Blackmore et al 2012 PNAS

Can the gene be introduced after the injury?  That was the next test.  There’s reason to believe that there’s some functional benefit.

What’s next?  “I don’t want to oversell this . . . what we have is a treatment that induces growth in a fraction of the total axons, and they grow only a few millimeters in a mouse.”

We need to combine this treatment with all the other options . . . a first step is to combine this with the pten gene suppression treatment you just heard about.  They’ve already checked to see if their treatment is duplicating the pten results, and the answer is no . . . which is good, because the combination then would be expected to work better.  What about overcoming the inhibition?  What if we add Chondroitinase? (more on this later)

We also need to take advantage of new technology . . . there’s a whole next generation of RNA sequencing, and the possibility of using induced pluripotent human cells, which the Miami Project is working on now.

Also, lets find other routes to new molecular targets.  He’s always looking at new data sets, and has his eye on another gene target called SOCS 11.

Finally, is there a useful convergence between cancer research and sci research?  He’s focusing on the transcription factors . . . there’s 12 that seem to have a role in axon growth.  On the cancer side, he did some data mining and found 210 that are involved in cancer growth.  How do they overlap?  Of the 12 that have already been shown to matter, 11 are also involved in cancer growth . . . whoa.  That means those other 199 suddenly become very interesting.  He’s looking at going right into animal testing with those.

What –finally– about chronic injury?  We know that axons at the injury site are not dead but dormant.  It’s possible that those neurons naturally vary in their ability to regenerate.  And we have screening technology that allows testing of large sets of genes.  And we know how to do viral mediated gene transfer that allows testing of gene function in vivo.

There’s reason for hope.

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One Comment on “Murray Blackmore”


  1. […] Dr. Murray Blackmore’s sheer cleverness, determination, and most especially, youth.  I’ve heard for a long time now […]


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