Cool Videos: Cytotoxic T Cells on Patrol

SO COOL!!!!!

NIH Director's Blog

Cytotoxic T Cell Video screencapture

Wow! It’s one thing to know that the immune system has the power to destroy cancerous cells. But it’s quite another thing to see a cytotoxic T cell actually take out a cancer cell right before your eyes.

This amazing video was produced by Alex T. Ritter as part of Celldance 2014, an annual video series by the American Society for Cell Biology (ASCB). To make this series happen in 2014, ASCB staff contacted cell biology labs known for their sophisticated imaging tools and techniques, asking them to submit proposals for videos. In return, ASCB provided some funding, post-production support from a professional videographer, and an original soundtrack from the up-and-coming Hollywood composer Ted Masur.

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The Poet-Scientist

It should be pretty obvious by now, if you are a functioning adult, that people are multi-faceted complex beings.  I am no different.  I am a scientist by training, yet a poet at heart.  For this reason, I’ve set up another blog called Thought Liquor.  So if you want to see the part of me that listened to My Chemical Romance in the not-too-distant past and watches The Nightmare Before Christmas on both Halloween and Christmas, then you should check it out.  By way of a preview, here is a piece I wrote that lies at a crossroads between science (the pharmaceutical industry) and poetry.  Enjoy!

Pharmacy is pharming doctors
Doctoring details of drugs described as
Definitively effective when the efficaciousness
Is definitively disingenuous.
They lure with lunches
Succor with samples
And, as is their intent
Prescription practices prosper
Into pharmaceutical pockets.
You might say a lunch is a lunch
But I’ve a hunch your eyes are scrunched
Against the whole picture.
Picture society as a web of give and take
Where what you make is not what you make
But is instead the reciprocal of taking.
That is to say the giving of a thing
Is not in the thing but in the giving
Because our cerebral oscillation is based
On societal implications which from
Roots indeterminate determined that
Without reciprocity our society will cease to be.
And since surprisingly MDs are human too,
This rule applies also applies to that select few.
So if pharma gives, doctors take,
then doctors prescribe
and patients take
then pharma makes
on the reciprocal of take
the end result is that
they rake it all in.
They’re the ones to win.

Academia, Windows XP, and Cyber Susceptibility

Blood, when it is separated by density and size, is actually beautiful.  Using an Oncoquick column, which optimizes circulating tumor cell collection, you can clearly see the layers: red blood cells filling the bottom, lymphocytes and (hopefully for me, but hopefully not for the patient) tumor cells in the middle gradient, and finally plasma and platelets skimming the surface in their yellow lipid glory.

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Blood separated in an Oncoquick column by density and size. The porous barrier (white) allows RBCs to slip through but keeps the bulkier cells above.

After harvesting the blue interphase for circulating tumor cells, I had to separate the tumor cells from the other cells that might be floating in the mix.  To do this, I used a process called fluorescence-activated cell sorting, or FACS.  This meant tagging my cells with fluorescent antibodies, then sending them through a gigantic machine one by one, where each would be flashed with light to see what antibodies were on them, then sorted into their appropriate populations.  This is a powerful tool that many scientists use to collect a specific type of cell.

Given the sensitivity of such a machine (it’s sorting single cells after all), as well as the sheer expense (upwards of $120,000, plus a trained technician to operate), you might imagine my surprise when I noticed the software running the machine WAS RUN ON WINDOWS XP.

That’s right.  Good ol’ XP, the longest running operating system Microsoft made, which is no longer supported.  That means computers running XP are more susceptible to malware and hackers, or, as Network World, a tech site put it:

When Microsoft stops supporting XP criminals will keep on finding new ways to exploit the operating system. The list of unpatched exploits will grow and grow to the point that compromising XP machines will be elementary for hackers. Data on XP machines will be at risk. XP machines on networks will become launch pads for internal attacks against better supported machines. They could easily be recruited into botnets to launch coordinated DDoS attacks or massive spamming.

The thing is, the FACS machine’s computer is not an anomaly, but a trend.  Everywhere you look in academia, the software running our most tried and true machines are running Windows XP, or even older!  The computer running my gel doc uses Windows 95!

"I've been trying to send an email for the past 10 years."

“I just got my AIM account!”

We do this because as scientists we adore reliability and replication.  It’s more than the maxim If it ain’t broke, don’t fix it; it’s more of “if it yields the same results every time THEN FOR THE LOVE OF GOD DON’T CHANGE ANYTHING!”  It’s hard enough to get two Western blots to give the same result using the same parameters, and if you go messing with something like software, which is often way beyond biologists’ ken, whole projects can go belly-up.

But what does this mean for us scientists? In the short-term, maybe nothing.  But think about this: many research labs are closely connected to hospitals which have sensitive patient information, or are running clinical trials themselves, which may have incredibly sensitive information.  When you are running computers with XP that are connected to an intranet, such as the Partners network used here in Longwood, the whole network is at greater risk because of those antiquated machines.  Thus, for patient privacy alone, updating the operating systems in research labs should be imperative.

There’s one problem though: most software that runs on XP won’t run on other operating systems.  So if you upgrade your OS, you may be left with a $150,000 FACS machine that you can’t use!  While bioinformatics may be booming, the software used to run our expensive equipment is usually developed by the companies selling it, and boy do they make the price tag reflect that.  The lack of opensource or inexpensive software for specialized laboratory equipment operation may end up bringing about a major cyber-security disaster.

Now, this is not nearly as dire a situation as our nuclear program using floppy disks, but it does not take a genius to realize that hospital networked computers should be running secure operating systems.  The sooner we take action, both as individual researchers and as a scientific community, the better.

Why the daily grind is different for scientists

In response to The Daily Post’s writing prompt: “A Moment in Time.”

“What was the last picture you took? Tell us the story behind it.”

The last picture I took was this:

mutant spine

What you see here is a cross-section of mouse spine. It’s not supposed to look like that.  For some reason, the mice in this model develop growths which protrude into the spinal column, limiting mobility, causing altered gaits, and in general doing more harm than good.

When we set out to make these mice, which have been bred for the specific purpose of causing mTOR activation of pericytes in the kidneys, we never intended for the above to happen.

This is not uncommon. This is science.

You have a hypothesis: that if you manipulate gene A in this mouse you will get phenotype B.  What actually occurs is a different matter, and one of the reasons I even have a job.  The issue remains, however, that your experiment is an animal.

When you are working with animals and altering their genetic makeup, you begin to become inured to the various phenotypes you may see around you.  For example, if working in a neuro lab, it may become run-of-the-mill to see mice seize (this has happened to me).

One mouse model I was reading up on ablated pericytes, which stabilize capillaries and other small vasculature.  These mice would die in 2 months from global internal bleeding.

Another mouse model I worked with, again, for a neuro lab, literally went insane.  It had no fear, due to improper amygdala connections, and would run around like it was on amphetamines before seizing.  These mice typically did not last longer than a month and a half.

We were trying to develop a model for facial angiofibromas for patients with TSC, and caused elevated mTOR activation in fibroblasts in mouse skin.  These mice would develop loose, flappy skin that would itch and tear easily.  They were literally uncomfortable in their own skin and at times would attempt to scratch it off.  Not to mention the females had a fifty percent chance of developing ascites at a late age.

We scientists do not just witness these vignettes of suffering, but think long and hard about how we will make it happen and how we will show it happened.  This wears on a person more than words can describe.

The daily grind of a scientist is looking at the image above, recognizing that you were the one to bring about this physical change which dominates how an animal views its world, and moving forward with trying to parse out the mechanisms by which it occurred.  All this gets processed, at some level, with each glance in the microscope, each mouse handled, and each manuscript submitted.

UC San Diego grad student Amay Bandodkar invents temporary tattoo that monitor diabetics’ glucose levels

This could be fantastic for diabetics! Props to the genius behind this: Amay Bandodkar.

Universal Journal Review

Science Alert: Engineers from the University of California, San Diego have developed an ultra-thin temporary tattoo that can painlessly and accurately monitor the glucose levels of diabetics.

The flexible device costs just a few cents and lasts for a day at a time, and early tests have shown that it’s just as sensitive as a finger-prick test.

But even cooler is the fact that the system works without blood, by extracting and measuring the glucose from the fluid in between skin cells, and could eventually be adapted to detect other important metabolites in the body, or deliver medicine.

CLICK HERE FOR ARTICLE

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The Future: Virtual Reality, Computational Biology, and You

Yesterday, I opened up my brand new 7 dollar Google Cardboard. This nifty little device, made of innocuous cuts of cardboard, a few magnets, and some lenses, can take any smartphone and convert it into a virtual reality device, similar to the Oculus Rift (though for a MUCH lower price). While there are still only a handful of apps available, and you can’t use it for too long before becoming a bit queasy, the potential of this device is incredible.

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You will get that look on your face when you first step into virtual reality.

Most of the apps you find are what you might expect: riding a virtual roller coaster, taking a virtual tour of the palace of Versailles, and even a rudimentary zombie first-person shooter. What really caught my attention though was an app called Orbulus. Users can upload 360 photos, which can be taken using any smartphone and Google Camera, which creates “photospheres.” If you step into one of these photospheres using Google Cardboard, it is as if you are standing exactly where the picture was taken. Last night, in the space of five minutes, I was looking at the glittering lights of the Eiffel Tower, then was transported to a tiny comic book shop in Tokyo. Each scene is incredibly immersive.

To me, this device, and really, the future of Virtual Reality in general, holds great promise for science and science learning. A huge difficulty facing teachers and students alike is the foreign nature of the cell; it simply is too small to see and comprehend. Imagine though, stepping inside a cell, looking up at a massive Golgi overhead, and watching as swirling enzymes crisscrossed before you in a bustle of productivity. The micro turned into macro through virtual reality. I get excited even thinking about it – imagine a child seeing the cellular world in it’s full glory – this is what inspires curious minds.

Source: http://www.dailymail.co.uk/sciencetech/article-2335596/Photographs-reveal-alien-planet-No--breathtaking-animated-simulations-world-HUMAN-BODY.html

Imagine this, several stories high, looming over your head, vesicles forming like bubbles from the bottom of a boiling pot.

Even further than aesthetics though, manipulation of objects in virtual space interests me. There are already a number of apps which allow you to view proteins in 3D from your smartphone (I use NDKmol). It should be a rather easy step to configure apps like these to be compatible with Google Cardboard and other virtual reality devices. Thus, you can see a protein, perhaps interacting with small molecules, like drugs or antibodies, in fully rotational three-dimensional space.

However, this is a very hands-off, non-interactive approach. You might notice that Google Cardboard has a slot for the front facing camera to be exposed. This may be to allow for apps to combine virtual reality with reality, such as superimposing Google Maps directions directly onto your field of view (through your front-facing camera). It also may be used for motion tracking of your hands, so that you can interact with your virtual reality using simple hand gestures.

So imagine being able to interact with a protein in virtual space, and, if you can code it robustly and efficiently, you may even be able to push and pull on residues and see how the whole protein might respond, conformationally, given the underlying chemical properties (i.e., charge and stereochemical configuration), to your virtual mechanical stimulus. This of course is heavily reliant upon computational biology, which is still tackling what may seem to be the most basic of challenges: how a protein folds. Strides are being made, however, and using these ideas, you could probe a protein for its weak points, potentially find targets of inhibition or activation, all simply through virtual manipulation.

These concepts are of course mere speculation, but the possibility is very real given the technology we have at hand. It may only be a matter of time before we can step into the cell, snag a whizzing protein out of the air, and unfold it to see how it is made.