UC Berkeley Cyclotron adventures!

Disclaimer: This post is a little nerdy, so if you don’t want to read or see nerdy things, I suggest you wait for the next post…

X-ray Protein Crystallography is a method in which scientists use x-rays to shoot protein crystals in order to determine the arrangement of atoms in the protein’s molecular structure. The process of creating these crystals is to use purified protein, certain binding ligands (ex. different drug compounds), different salt solutions, and a constant environment. Very similar to making rock sugar candy, the crystals form in supersaturated solutions that range in volume from 1 to 3 microliters (uL). The process for crystals to form can range from a few days to months.

Due to the small environment that the crystals are grown in, the crystals themselves are microscopic, and very rarely seen by the naked eye. In order to shoot the crystals with x-rays, we utilize miniature loops to catch the crystals. Instead of facing the elements that the cowboys’ of old endured, dust in the air, the possibility of a stampede, we as modern day researchers must combat the dreaded surface tension, the conditions crashing out and forming gigantic salt crystals, and the bitter cold of liquid nitrogen (-321 F!). Side note, your body temperature is so much hotter than liquid nitrogen’s that if you were to stick your hand in liquid nitrogen, the liquid nitrogen would evaporate before even touching your skin. The only time where you get hurt from liquid nitrogen is when it cools something else that you’re touching, for example a metal wand, or your clothes. However, all the science facilities still require you to wear long pants, safety googles, special gloves, and close toed shoes, all in the name of safety I guess…

So using the microscopic loops and finally catching a crystal, we immediately put the crystal into liquid nitrogen and into a ‘puck’ system. Before, everything was done manually, so each loop has its own capsule that protected the tip holding the loop and keeping it immersed in liquid nitrogen, but now the cyclotron is updating their systems and prefers the use of the pucks. Once we have the crystals safely in the loops, we put them into the machine where we have to align the cross hairs to hit the crystals at a full 360 degree rotation to get all the data. This is difficult due to the orientation of the loops on the pins, the size of the crystals, and the distorted optics due to the shape of the drop on the loop. Remember how when you put a straw into a cup, it doesn’t go in a straight line? That’s pretty much what we have to deal with when we’re shooting microscopic crystals.

If we successfully aligned the crystals, and have enough diffraction (usually 2.8-3.0 angstroms), then we proceed to gather data at the full 360 degrees. This process usually takes 30-45 minutes. We then save the data and process it when we get back to San Diego. Why go through all this work to find the molecular structure of a compound you ask? Well, researchers have a basic idea of what the compounds would look like, but the data that we gather is a verification/correction of what molecular structural chemists initially thought. Another reason is to see how the ligand binds to the binding pocket of the protein, which will allow us to design future drugs to fit better and be more effective.

A little bit about the lab I work in, I work for Palmer Taylor, Dean of the Skaggs School of Pharmacy. He has been doing research before the 60’s and is still one of the leaders in the field. The focus of our research are the nicotinic and acetyl choline receptors in cells, and the main purpose is to ultimately create cures and treatments for diseases and afflictions that deal with those pathways, such as Alzheimer disease, nicotinic addictions, myasthenia gravis, and more. But the reality of research in academia is that its difficult to work with collaborators and with profit not being the driving factor, research sometimes proceeds at a snail’s pace. Though, industry isn’t always as productive. If a company created a cure for a disease, they wouldn’t make as much money, as opposed to a treatment that requires patients to constantly be purchasing drugs from the company.

Just to give you an idea what researchers get charged for doing all this science-y stuff, pins themselves cost 3 dollars each, and we use 16 pins per puck (425 each), and 7 pucks per shipping cane (1250, and 1 shipping dewar (475). That’s 5036! However, that’s not the most expensive part…the beamtime that we get at the cyclotron is 20,000 for a single shift (8 hours) on a single beam. Our trips typically last 2 days, which means that if we were industry, our trip would have cost 120,000 without a guarantee of collecting data! Although, we have done trips for 3 days, and had 2 beams at once, so you can do that math. The reason why it costs so much is the machines used to sense the X-ray diffraction cost 3 million dollars, there are maintenance fees, employee salaries to pay, and finally, just because it’s ‘research,’ you can slap on an extra few thousand dollars. It’s all your tax dollars at work, since research is driven by government funded grants.

During our trip 1/15-17/11, the weather was amazing, the sun was out, everything was comfortable. This recent trip, 2/18-19/11 had crazy amounts of rain, and who knew that the Berkeley hills could get so cold? While we were working, it started snowing, to the point that my supervisor and his kids were able to make snowballs and pelt each other with those bone-chilling balls of doom. Anyways enough of my blabbering, enjoy some pictures!

Very dangerous conditions...

Pins and Pucks

Example of crystals in a loop

Machines, materials, and robots

Old school cyclotrons

Thanks for looking!

Maybe I can get Southwest to sponsor me since I fly with them so often…

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