Of Oncogenes And Target Cells...

Bipotency
UberAllesVille


I started gradual school 40 years ago.

Luckily for me, a very smart woman agreed to let me come and work in her lab to try and figure out if subtle differences in a target cell would affect the type of cancer you would produce after you introduce a powerful 'oncogene' into those cells.

We chose cells from the outer part adrenal gland as the targets because, as they develop down a 'lineage', they exhibit subtly different characteristics that based on the type of steroids they synthesize and secrete.

When I started this work I had know idea that I would actually spend the first few years first isolating, then separating, and, finally, characterizing those different steroid-secreting target cells.

Then, in the end, I had to figure out how to keep the different cell types alive in a culture dish so that I could whack them with a nasty little bug called the Kirsten Murine Sarcoma Virus.

Why?

Because the genome of that virus codes for a very strong oncogene called K-Ras.

And the product of the K-Ras oncogene is an oncoprotein that turns all kinds of target cells into tumor cells when you ram it into them experimentally.

And why does it do that?

Because the oncoprotein interacts with and 'turns on' a series of signaling proteins located inside the cell that drive the uncontrolled division of that cell.

And it turns out that the K-Ras oncogene is also present in a large number of real (i.e. not just experimental) tumours in actual people, including the most aggressive, hard-to-treat, and very often deadly, pancreatic cancers.

You may have read or heard about a recent 'breakthrough' treatment for aggressive pancreatic cancer that involves the use of a revolutionary new drug.

As you might imagine given the set-up here, that drug blocks the activity of the K-Ras oncoprotein.

We'll discuss how that works next time. It's really quite ingenious and, to foreshadow things a little, the drug acts by preventing the interaction of the oncoprotein with almost all of those signaling proteins that drive cell division in the ontogenically-transformed tumor cell.

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Image at the top of the post?...Individual rat adrenal cells that can either become steroid secreting or goopy matrix producing cells sticking to the bottom of the culture dish. Because they can produce two cell types we described these cells bipotent and stem-like...The little bright, black-rimmed spots that are packed into most of the cells are actually tiny droplets of lipid that hold the cholesterol that forms the chemical backbone of steroid hormones.

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Back In Bow River, Again.

WakeUpBluey
You'llMissBrizzy


I've been doing a lot of old mannish stuff recently.

This includes helping my brother, who is doing all the heavy lifting, take care of our ailing Dad.

As such, I've been going to and from the Republic of SouthVanIsle most weekends.

Which means a whole lot of commuting by boat.

Which further means that I've been listening to a lot of musical playlists on the evil streaming service, particularly when I'm riding in to our fine province's capital city from the Swartz Bay ferry terminal.

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Now.

The best of these playlists arrive by way of my youngest kid, who, as I've mentioned here before, keeps me up to snuff on all things new and happening.

Which is why we're going to see another young kid named Julia Jacklin, live and in-person, in the fall.

But, as an old guy, sometimes I can't help but build my own mixtapes, errrr, playlists.

And, as you might imagine, these lists are often larded with personal aural nostalgia.

And one group I've been overdosing on quite a bit these days is called 'Cold Chisel'.

Like Ms. Jacklin, the Chiselers are from Australia. 

Unlike Ms. Jacklin, the Chiselers hit their peak in the early 1980's before they imploded spectacularly, pretty much for good.

At least creatively because, as you might have guessed, their filthily lucred reunion tours are never ending.

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I've never been to the Bow River that is located in northern most West Australia.

But I did spend a few months vagabonding around the 'Struth Island, mostly in a used Holden HD, with my friend S. in the second half of 1981 and the first bit of 1982.

And while we spent the first few few days of the latter year trying to learn how to surf on a beach not far from Australia's southernmost tip that is festooned with the so-called 12 Apostles, we rang in the New Year at a concert in Melbourne watching, you guessed it...

Cold Chisel.

They were a powerhouse of blues-infused rollicking and rolling pub rock with a hulking, stage-stalking Jimmy Barnes on vocals, masterful Ian Moss on guitar, a wicked rhythm section, and the maestro, and chief songwriter, Don Walker way at the back, stage right, on keyboards.

Anyway...

Whenever, I listen to to their song titled 'Bow River' I am immediately transported right back to that time and place when I discovered the group while simultaneously doing and thinking all sorts of young man not-so bluesy, because-everything's-rosey-not-grey-and-out-in-front-of-you-type things.

Gosh.

It really is incredible how music can do that to you.

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In a weird way Chisel is Australia's version of the Tragically Hip, massively popular at home but no matter how hard they tried they both failed miserably in their attempts to crack the American market.
SubHeader?...At the start of our sojourn we landed in Sydney and immediately took a bus out to the end of the line going north (which is another Chisel lyrical trope) because we'd been told that was a good place to start hitch hiking...And it was...Our final ride got us to Brisbane, which is where we plunked a few hundred dollars down on our super reliable Holden HD, which looked kind of like a late 60's Rambler sedan...Anyway, during that last hitch trip one of the other passengers was a young red haired kid that the car's driver kept calling Bluey, which is apparently the Australian version of the Irish 'Ginger' designation for folks of that fiery follicular hue...Brizzy is, of course, slang for Brisbane...They shorten pretty much everything down there  and stick a 'y' or and 'ie' on the end of it.
Thanks so much to reader EG for prodding me into doing the editing and publish button pushing on this one...It had been sitting in the queue for a few weeks now. 

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