Future Ben

First off I want to be clear that I didn’t expect to win the young investigator’s award. OK, I am still bitter about it, but I am bitter about lot’s of stuff. So while I am not particularly upset about not winning, it was the finalists who really irritated me.

All three featured commercial products some with affiliation to the “judges.” That really set the tone. Sure there is no point in reinventing the wheel, but using something you bought as directed by the manufacturer is not exactly ground breaking. To her credit the winner was actually collaborating with a chemist to improve the agent. La di frigging da.
None of the finalists used any methods other than imaging. Sure it’s an imaging conference, but if you are going to claim your labeled differentiated into a particular type of cell, you are obligated to back that up with some staining. “We injected some bone marrow, it did aomething, you can see it, isn’t that awesome?” Wow, mail that back to 1988 when it wasn’t taught in first year immunology!

So what was the judging criteria. judging from the abundant use of the RGD peptide for labeling avbeta3 integrin, it was mostly based on FDA approved nonthreatening tech. By nonthreatening I mean it doesn’t challenge anybody’s research. To set such a conservative standard for grad students and post docs is a travesty. This is the point in our careers where we should be challenging the status quo or at least looking at biology in a new way. Sadly, medicine is too parochial and corrupt to allow real creativity to flourish.

I am back in construct design mode, and a deeper lesson just dawned on me. I have been playing with a human protein in a human cell. It’s the metal transporter DMT1 that I will be talking about in Kyoto next week. Not surprisingly, this protein is tightly regulated at every level. How do I get around that problem?

I could edit out parts of the sequence and figure out what parts are regulatory, but that could take a long time. It turns out that a long time ago E.coli picked up the gene for DMT1 through horizontal gene transfer. All the regulatory parts have long since mutated away. Thanks for the help. I am going to use the Bacterial protein as a starting point, but of course it’s not that simple. First off bacteria prefer to use different codons for proteins. you can still get bacterial genes to express, they just don’t do it very efficiently. i have to synthesize the gene for mammalian expression. That’s not so tough these days. A trickier problem is the membrane. E.coli have a different thickness of membrane than a mammalian cell. I will have to do some serious sequence gazing and mental modeling to fix this problem. Sadly there is no structure to work with. If there was somebody else would have done this already.

Damn I have to geek out here for a minute. I am listening to this dude give a tlk on the lambda repressor. It’s been 20 minutes of rambling about how life is just mass action and kinetics. He has the smug confidence of a man who doesn’t know how dated he is. Denying Systems Biology is the new Inteligent Design.

Seriously, just because you figured out that the Cancer field is mostly bullshit doesn’t make you Linus Pauling!

Now Len Girrenti is talking about Sirtuins. Makes sense that Sir2 in year and worms points to a working Sir2 in humans.
“I don’t know of caloric restriction will make you live longer, but it will sure feel like it did”. Ha!

I guess the whole point of taking resveratrol is to pretend like you are living like a yogi. Awesome!

Sirt1 stimulates BDNF production. Who is taking a systems approach? There must be a bunch of people.

It makes me think about going all out on aging. That field is never going away.

It’s a rainy day. When it’s like that outside I find little things to do around the lab.

I have a series of surgeries next week so I better get all my scissors sharp and organized!

I finished running all of the gas lines for a new oxygen enriched anesthetic system. Once the last part was in place I had to step back and get a picture.

Techically not steampunk, but all the gauges and pneumatic hoses next to the superconducting electromagnet reminded me of a panel from Girl Genious.

Next I will install a tesla coil and a giant knife switch.

After months of failure. I finally succeeded in electroporating my novel reporter gene into the brain of a newborn mouse. As it turns out the equipment I was using was crap, and since I don’t know anything about unipolar square pulses with exponential decay, I was unaware of its shortcomings. So after ~250 mice injected that sacrificed. Here is the result.

The champagne doesn’t pop just yet however. This wasn’t what I was going for. Getting GFP to express like this was an achievement a few years ago, but it is just the control for my real experiment. The question is, does this correlate to an MRI? I have a whole litter of these pups, and hopefully the other 9 have the same kind of expression as the 3 who were sacrificed so far.

But, if they really do correlate, suddenly it is endgame for my thesis and I can start doing some cool stuff with the my new technology.

I have made 9 lines of transgenic mice. The idea is these mice are expressing GFP and my synthetic MRI reporter gene. We are at line 3 with no sign of expression.

I know transgenic mouse technology is not very reliable, but I am braceing myself for the worst case. I added an extra feature above and beyond what a normal transgenic DNA construct warrants. I fear the cost of my futureization habit will be epic fail.

It is in my nature to meddle with elements beyond my understanding.

I have been appointed the task of naming my first foray into synthetic biology/ protein engineering. I have never invented anything substatial enough to name before so I am having some trouble.

The protein is a new reporter for MRI. It binds paramagnetic Manganese and it creates a brighter signal than background tissues when imaged properly. What the hell do you call something like that?

My coleague and friend Yousef had this to say.

your construct could
termed as MP’s standing for either “magnetic protein”, “manganese protein”,
“metal protein”, “MRI protein” (a lot to stand for) to parallel the FP field
(fluorescent protein). Since there is no color such as in GFP and RFP
etc….Your enhanced MP (EMP) are reduced to 2 tone: darkening (DMP)and
brightening (BMP)proteins. In DMPs Ferritin would be one of them and in BMPs
yours would fall in this category…

BMP? I’m not sure it has pizzaz. Although I agree that an acronym would be appropriate. How about Manganese Enhaced Magnetic Resonance Imaging Protein? MEMRIP. Maybe MRI can be collapsed and I could just call it MEMP. If I did and Iron one it would be FEMP.

I have to figure this out before starting the patent.

Dude I don’t even know where to start. On the surface it’s not really that much of a crackpot site, it just has the all the standard layman’s freaky science highlights. Nothing about Atlantis, but what the Brazillian Stonehenge has to do with the future I don’t know. Maybe the dude is right and Light Transformation is going to be the single most important scientific theory of our time. Although its not so much of a theory as a series of wandering “what if” statements based entirely on handwaving and misderstood generalizations. ( I knew the spite would kick in)

So why on pick on somebody else’s vanity site which is also based loosely on science and the future. It’s a matter of priciple! There is a real danger in presenting your assumptions along with a little data. This website is the result. What kind of reference is the fucking Book of Knowledge: The Keys of Enoch? Who peer reviewed that? Actually, I am noticing most of the citations are largely self referencing. Of the few links that acutally work my personal favorite is this statement on the martian pyramids.

Pyramid structures which range in dimensions of 3.0-base to 6.0 km mean diameter have been identified in the Elysium Quadrangle of Mars. Geologic processes that could result in such features have not produced a satisfactory scientific explanation for some of the pyramids. Thus we must keep in mind that what may appear to be a natural hill from an aerial view may be a pyramidal artifact.

Perhaps, instead of preparing for the contemporary scans of the Martian micro-intelligence, we might prepare ourselves for a close examination of pyramidal structures as blueprints for bio-magnetic analogs? The Martian and Egyptian pyramidal grids may be models preparing us to meet the superior architects in our immediate universe? Perhaps, the pyramid is a future artifact?

And all this is based on what data?

OK…So based on this image alone, not only does Mars have pyramids from the future, any hill on Mars could be actually be a pyramid in disguise that might “hold the keys to man’s existence.” This dude comes right out and says that we should beleive that a bunch of piles of sand are magical because it would be awesome if they really were. Get over yourself!

Everybody wants to believe there is a pot of gold at the end of the rainbow and that all of our questions will be answered if we can just get over the horizon. And let us not forget that old chestnut. Everything you know is wrong, but I have got it all figured out, so come join my clique of people who know what’s really up. I would like to make through at least one Burning Man without having to hear a variation on that one.

But what if they really were pyramids? That would in fact be awesome.

What the hell am I supposed to do with that? I have spent a large chunk of my day trying to figure out another of these little puzzles and it has left me rather cross. In fact I have spent at least a dozen hours over the past few days trying to pick apart other people’s cryptic little maps. This is the promoter/enhancer of Flk1, some receptor that does I don’t know what. The point is that this sequence will cause expression in developing vascualture. The key word here is SEQUENCE. Why am I looking at a crude line drawing when they could just post a text file? No, instead I have to Genbank and BLAST my way through the mouse genome looking for the right piece of DNA then take my best guess at what they cut out. Did they not know the sequence? I guess this stuff came out in 1995 so it wouldn’t be surprizing.

I remember an a review paper about Genomics being, “too much information” to be useful. Give us our bright and shining gel bands of approximate size! Luddites! I dig through notebooks of paper notes, pictures, crude maps all for one text file worth of information. And the actual DNA is nowhere to be found. Its a wonder anything ever got done that way.

So here I am, doing reverse bioinformatics to digitize what has already been published. Compiling my sequences in VectorNTI and creating dynamic maps that have more information that I am going to use, which is just about enough.