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Lawrence Berkeley Laboratory Field Trip
#1
REPORT FIELD TRIP on March 28th 2013:
LAWRENCE BERKELEY LABORATORY FIELD TRIP
Student reporter: Katherine Miller, Biotech Club, CCSF

Tuesday, April 2, 2013

Dear fellow club members,

I would like to represent all the students and staff instructors in the field trip group from the CCSF Biotech Club to thank Doctor Corie Ralston, Doctor Simon Morton, and Dr. Peter Zwart, who gave our group the opportunity to witness the fascinating giant synchrotron system, the Advanced Light Souce (ALS) at Lawrence Berkeley National Laboratory. The ALS generates forty beam-lines, each of which is used for a different application. I also want personally to thank Rebecca D’ Urso, the field trip coordinator who had thoroughly prepared the tour, leading to its success.

The group gathered at the conference room 2202 on the second floor of building 6 of Lawrence Berkeley National Laboratory. We had a thirty-minute brief introduction with short video illustration of one of the most fascinating applications of synchrotron and its beam-line system: crystallography.

Crystallography is an essential technique to image 3-D structure of proteins. To understand why it is essential to know protein 3-D structures, we need to understand what proteins are and why they are so important in biotechnology and how they relate to the pharmaceutical industry.

Proteins (their four main atoms are linked together with multiple linkage styles between carbon, hydrogen, oxygen, and nitrogen, in addition with numerous of other atoms such as sulfur, iron, zinc, copper, etc.) in biotechnology field, are the huge bio-molecule with myriad bio-functions depending on their myriad shapes. Their shapes, in 3-D structures, are too convoluted and small to photograph by the technique of regular X-ray imaging. That is why synchrotron, the high-energy magnetic field circular system, generates electron beam; then, the beam-line system is one of the end-points that take up this high energy beam to create high-fidelity-X-ray beams at the level of photon-beam that can increase the signal-to-noise level more than thousand times that of non-synchrotron X-ray sources. Once diffraction data is collected on a target protein, its structure into the level of their atoms and their linkages can be solved.

In the pharmaceutical industry, a protein found is often the target for patho-physiology cause of a disease. Researchers try to make other proteins to either activate or inactivate this protein depending on the practical reason of the treatment for that disease. For example, incretins are a group of gastrointestinal hormones to increase the body’s sensitivity to insulin (a pancreas protein) in the treatment of diabetes mellitus. Activation of incretins by creating a linkage or breaking a linkage in their structure would lead to the increased sensitivity of the body to insulin. Incretin is made into a drug for this purpose.

How to do crystallography on a protein? Dr. Ralston instructed the group to create crystals of lysozyme, a cell enzyme for cleaning up debris inside cell matrix. Once protein crystals are made, they will be frozen in liquid nitrogen and transferred to the beam-line for imaging its structure. The beam-line has robot arms that can accurately fish up the crystal hook pockets and positions it in front of the beam-line ending box right in front of the diffraction detector camera for snap-shot one by one, and then the diffraction images are transferred into the computer system where a scientist interprets the result and determines the protein structure. Multiple snap-shots of the crystals of the same protein are generated and the more accurate image is extrapolated by the computer system.

Doctor Ralston explained that Lawrence Lab takes contracts with many pharmaceutical companies for using the beam-line system for their target proteins in their new drug manufacture, and that is paid-service contract for at least a few years for one drug! Lawrence Berkeley National Laboratory, though independently operates from UC Berkeley, has some collaborative and supportive activities in academics and beam line researches with UC Berkeley to a certain extent.

The synchrotrons system is also essential for high-tech discovery in other fields; the beam line can also be used in tomography, in imaging computer chips, etc. There are four nationally-funded synchrotrons in the US, two in California, one in Chicago, one in Long Island. There are also many synchrotrons around the world; a few are built in China, Europe, etc. These are often national and government funded system; however, private smaller synchrotrons with less investment dollars can be built separately from a large-scale synchrotron which is a multi-million dollar investment. Stanford has built an even brighter X-ray source called LCLS, which stands for Linac Coherent Light source.

The tour ended half an hour later than planned because everybody was so interested in asking many questions.

Thank you again Dr. Ralston, Dr. Morton, and Dr. Zwart and all of their staffs have given us a great opportunity to learn about this fascinating technology.

VIDEO LINKS:
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FOR YOU, who love art and technology,

The Lotus
What is prettier than the Lotus in the pond?
Green leaves, white petals, inserted by yellow pistils
Yellow pistils, white petals, green leaves,
Though living in the mud, the Lotus never stinks!
(Foreign language poem translated into English by Katherine Miller, June 2011)

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