Friday, March 16, 2012

Post Lecture Recap

Last night, I headed to the beautiful Bell House in the Gowanus section of Brooklyn for the monthly Secret Science Club lecture featuring molecular geneticist Dr Alea Mills of Cold Spring Harbor Laboratories.

Dr Mills began her talk with a discussion of the roles of P63 and CHD5 in cancer- both P63 and CHD5 are tumor suppressors. P63 is also essential to proper development and plays a role in stem cell replenishment. Using genetic engineering techniques, the P63 gene can be deleted, and the altered gene can be injected into a blastocyst to produce a chimera- chimeric mice with a P63 deletion fail to develop proper.

The CHD5 gene is also a tumor-suppressor, it prevents tumor development and fosters apoptosis (cell death). The Ink4/Arf locus is turned on by chd5 deletion in human glioma and other tumors. Dr Mills indicated that the full role of the mutation is currently unknown- is it the "driver" or a "passenger"?

Dr Mills finished with her discussion of tumors, and spoke about experiments with mice seeking to discover the role of gene deletion in autism spectrum disorders. Gene 16p11.2 is a region the 16th chromosome. 16p11.2 deletions can be de novo mutations- they are typically not hereditary. The genetic engineering techniques used in studying 16p11.2 deletions are similar to those described in the p63 deletion studies- the altered gene is injected into a blastocyst to produce a chimera.

Approximately half of the mice with 16p11.2 deletions die shortly after birth. Surviving mice with 16p11.2 deletions show non-progressive behavior- they tend to have trouble adapting to novel conditions (different cages). They engage in repeated, restricted, "ritualistic" (one particular mouse would "dismount" from the cage ceiling in a particular fashion) behavior. The "autism mice" exhibited hyperactive behavior and had sleep deficits. The hypothalamus in the autism mice is altered. For a good overview of the behavior of autism mice, with an interview with Dr. Mills and a link to a relevant video, this article in The Scientist can't be beat. Dr Mills stressed that there is no single cause for autism, but the study of 16p11.2 deletions was one factor in getting a more complete picture.

In the Q&A afterward, some bastard who likes to pry into the private lives of mice asked if the mice had problems breeding. The autism mice seemed to copulate without problem but, as noted, about fifty percent of the offspring soon died.

Once again, the lecture was top-notch. Not only was the lecture informative with regards to the subject matter, but it also gave a beautiful view of a working scientist's techniques, plus bonus mouse videos.

6 comments:

Aunt Snow said...

These Secret Science Clubs sound fascinating. I remember the summer we visited Brooklyn you urged us to go to one, but we were too tightly scheduled. Maybe the next time I come back to NYC.

Big Bad Bald Bastard said...

It's a great series. It's a good vibe too- a very diverse crowd, all united in a spirit of intellectual curiosity.

When next you visit, let me know- I hear there's a great baby biergarten in downtown Brooklyn.

Smut Clyde said...

I gets a bit itchy about "mouse autism models" after Mady Hornig announced in 2004 that she had produced 'autistic mice' by exposing them in puphood to mercury. Her research was paid for by those anti-vaccination nutbars who blame autism on the trace elements of mercury used in some vaccines, but never mind.

A number of people wondered how 'autism' -- a condition defined by impairments in social behaviour -- could be assessed in animals that aren't social. Hornig's mice had repetitive behaviour, which is seen in some autism cases but is not a diagnostic trait... in humans it's a sign of frontal-lobe dysfunction (also seen in schizophrenia).

Eventually someone pointed out that more than anything else, Hornig's mice showed the signs of pervasive peripheral nerve damage.

So what I'd like in an animal model of autism is not just a stretched analogy between human and murine behaviour, but also some of the neurological markers -- like the Purkinje neurons in the cerebellum being all cattywumpus. Dr Mills may well have covered this. Gonna read her article now.

Big Bad Bald Bastard said...

gets a bit itchy about "mouse autism models" after Mady Hornig announced in 2004 that she had produced 'autistic mice' by exposing them in puphood to mercury. Her research was paid for by those anti-vaccination nutbars who blame autism on the trace elements of mercury used in some vaccines, but never mind.

There are good-faith actors, and there are bad-faith actors. Dr Mills didn't seem to have any woo-based axes to grind.

Smut Clyde said...

OK, reading her interview and her paper in PNAS, Dr Mills has checked out neurological markers, and her mice do differ from normal in the size of their hippocampus. Which (as any fule kno) is a recurring finding from studies of autism.
So I rate for her work...

Big Bad Bald Bastard said...

Thanks for the quick review.
We drinking types don't like no Woo.

Cold Spring Harbor has a stellar reputation.