One of the earliest widespread applications of precision medicine in cancer care is helping patients and physicians decide whether chemotherapy is needed, a new study finds. Researchers looked at a test available to help assess the risk of breast cancer recurrence and whether chemotherapy i ... more
Vitamins doing gymnastics: Scientists capture first full image of vitamin B12 in actionWork by University of Michigan and MIT team yields new understanding of crucial reaction in the body and in CO2-scrubbing bacteria
You see it listed on the side of your cereal box and your multivitamin bottle. It's vitamin B12, part of a nutritious diet like all those other vitamins and minerals. But when it gets inside your body, new research suggests, B12 turns into a gymnast.
In a paper published in Nature, scientists from the University of Michigan Health System and the Massachusetts Institute of Technology report they have created the first full 3-D images of B12 and its partner molecules twisting and contorting as part of a crucial reaction called methyltransfer.
That reaction is vital both in the cells of the human body and, in a slightly different way, in the cells of bacteria that consume carbon dioxide and carbon monoxide. That includes bacteria that live in the guts of humans, cows and other animals, and help with digestion. The new research was done using B12 complexes from another type of carbon dioxide-munching bacteria found in the murky bottoms of ponds.
The 3-D images produced by the team show for the first time the intricate molecular juggling needed for B12 to serve its biologically essential function. They reveal a multi-stage process involving what the researchers call an elaborate protein framework – a surprisingly complicated mechanism for such a critical reaction.
U-M Medical School professor and co-author Stephen Ragsdale, Ph.D., notes that this transfer reaction is important to understand because of its importance to human health. It also has potential implications for the development of new fuels that might become alternative renewable energy sources.
"Without this transfer of single carbon units involving B12, and its partner B9 (otherwise known as folic acid), heart disease and birth defects might be far more common," explains Ragsdale, a professor of biological chemistry. "Similarly, the bacteria that rely on this reaction would be unable to consume carbon dioxide or carbon monoxide to stay alive – and to remove gas from our guts or our atmosphere. So it's important on many levels."
In such bacteria, called anaerobes, the reaction is part of a larger process called the Wood-Ljungdahl pathway. It's what enables the organisms to live off of carbon monoxide, a gas that is toxic to other living things, and carbon dioxide, which is a greenhouse gas directly linked to climate change. Ragsdale notes that industry is currently looking at harnessing the Wood-Ljungdahl pathway to help generate liquid fuels and chemicals.
In the images created by the team, the scientists show how the complex of molecules contorts into multiple conformations - first to activate, then to protect, and then to perform catalysis on the B12 molecule. They had isolated the complex from Moorella thermoacetica bacteria, which are used as models for studying this type of reaction.
The images were produced by aiming intense beams of X-rays at crystallized forms of the protein complex and painstakingly determining the position of every atom inside.
"This paper provides an understanding of the remarkable conformational movements that occur during one of the key steps in this microbial process, the step that involves the generation of the first in a series of organometallic intermediates that lead to the production of the key metabolic intermediate, acetyl-CoA," the authors note.
Senior author Catherine L. Drennan from MIT and the Howard Hughes Medical Institute, who received her Ph.D. at the U-M Medical School, adds, "We expected that this methyl-handoff between B vitamins must involve some type of conformational change, but the dramatic rearrangements that we have observed surprised even us."
- University of Michigan
- vitamin B12
A new molecular gel recipe developed at the University of Michigan is at the core of a prototype for a more accurate lead paint test. The test makes it easy to see whether a paint chip contains more than the regulated 5,000 parts per million of the poisonous metal that was banned from pigme ... more
Think your DNA is all human? Think again. And a new discovery suggests it's even less human than scientists previously thought. Nineteen new pieces of non-human DNA -- left by viruses that first infected our ancestors hundreds of thousands of years ago -- have just been found, lurking betwe ... more
A new molecular gel recipe developed at the University of Michigan by Anne McNeil, Arthur F Thurnau Professor of Macromolecular Science, and is at the core of a prototype for a more accurate lead paint test.The new test is more clear and accurate than its counterparts. It consists of a vial ... more
Serotonin is a neurotransmitter that's partly responsible for feelings of happiness and for mood regulation in humans. This makes it a common target for antidepressants, which block serotonin from being reabsorbed by neurons after it has dispatched its signal, so more of it stays floating a ... more
Choosing the best treatment for a cancer patient is often an inexact science. Drugs that work well for some patients may not help others, and tumors that are initially susceptible to a drug can later become resistant. In a new approach to devising more personalized treatments, researchers a ... more
Researchers at MIT and elsewhere have developed a new combination of methods that can provide detailed information about the microstructure of polycrystalline metals. Such materials — composed of a random matrix of multiple small crystals rather than one single large crystal — are widely us ... more
- 1Portable smartphone laboratory detects cancer
- 2Imaging technique maps serotonin activity in living brains
- 3The gene of autumn colors
- 4Sartorius Continues to Grow by Strong Double Digits
- 5Precision medicine test helps guide breast cancer patients' chemotherapy decision
- 6DNA damage response protein
- 7Agendia expands its business activities in Germany
- 8Ionic liquids simplify laser experiments on liquid samples