Circadian rhythms go both ways: in and from retina

Removal of Bmal1 accelerates the deterioration of vision that comes with Read more

Genomics plus human intelligence

The power of gene sequencing to solve puzzles when combined with human Read more

'Master key' microRNA has links to both ASD and schizophrenia

Recent studies of complex brain disorders such as schizophrenia and autism spectrum disorder (ASD) have identified a few "master keys," risk genes that sit at the center of a network of genes important for brain function. Researchers at Emory and the Chinese Academy of Sciences have created mice partially lacking one of those master keys, called MIR-137, and have used them to identify an angle on potential treatments for ASD. The results were published this Read more

Nobel Prize

Toe in the water for Emory cryo-EM structures

Congratulations to Christine Dunham and colleagues in the Department of Biochemistry for their first cryo-electron microscopy paper, recently published in the journal Structure.

The paper solves the structure of a bacterial ribosome bound to a messenger RNA containing a loop that regulates translation. This process is important for the study of several neurological diseases such as fragile X syndrome, for example.

Christine Dunham, PhD

Dunham writes: “We are focusing on establishing this in bacteria to understand frameshifting and protein folding as a consequence of codon preference. We will then build up our knowledge to potentially study eukaryotic translational control.”

The paper neatly links up with two Nobel Prizes: the 2017 Chemistry prize for cryo-electron microscopy and the 2009 Chemistry prize for ribosome structure, awarded in part to Dunham’s mentor Venki Ramakrishnan. Also, see this 2015 feature from Nature’s Ewen Callaway outlining how cryo-EM is a must have for structural biologists wanting to probe large molecules that are difficult to crystallize.

Construction now underway in the Biochemistry Connector will allow installation of microscopes (worth $6 million) necessary for Dunham and others to do cryo-EM here at Emory, although she advises that it will be several months until they are photo-op ready. For the Structure paper, Dunham collaborated with George Skiniotis at University of Michigan; he recently moved to Stanford. Read more

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Nobel Prize for place cells + grid cells

Congratulations to John O’Keefe, May-Britt Moser and Edvard Moser for receiving the 2014 Nobel Prize in Medicine. The prize is for discovering “the brain’s navigation system”: place cells, cells in the hippocampus which are active whenever a rat is in a particular place, and grid cells, cells in the entorhinal cortex which are active when the animal is at multiple locations in a grid pattern.

Former Yerkes researcher Beth Buffalo and her graduate student Nathan Killian were the first to directly detect, via electrode recordings, grid cells in the brains of non-human primates. Buffalo is now at the University of Washington and Killian is at Harvard Medical School.

A significant difference about their experiments was that they could identify grid cells when monkeys were moving their eyes, suggesting that primates don’t have to actually visit a place to construct the same kind of mental map. Another aspect of grid cells in non-human primates not previously seen with rodents is that the cells’ responses change when monkeys are seeing an image for the second time.

Following that report, grid cells were also directly detected in human epilepsy patients. The Mosers themselves noted in a 2014 review, “It will be interesting to see whether the same cells that respond to visual movement in monkeys also respond to locomotion, or whether there is a separate system of grid cells that is responsive to locomotion.”

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Look, don’t touch – noninvasive biochemistry

Much of the time in biochemistry, when you want to know what’s happening inside a cell you have to break them open.

Fluorescent proteins are a great tool and deserved their Nobel Prize. But you have to convince your favorite cells to make the fluorescent proteins first. It’s possible to think of specialized non-invasive probes too: dyes that change color when they encounter calcium, for example.

Now imagine being able to decipher what’s going on inside cells simply by looking at them and watching the proteins and organelles shift in response to signals. That’s essentially what Yuhong Du and Haian Fu at the Emory Chemical Biology Discovery Center have been able to do.

They use an “optical biosensor” which puts cells in front of a reflective grating. Depending on how the grating reflects light, they can measure mass redistribution inside the cells.

How the optical biosensor works

How the optical biosensor works

With this technology, they could watch for responses as cancer cells responded to signals from EGFR (epidermal growth factor receptor).

Drugs such as gefitinib and erlotinib are supposed to block those growth signals in lung cancer cells, but not every cancer responds to them. These results suggest that the optical biosensor system could be used to screen for compounds that block EGFR and many other receptors, potentially speeding up the hunt for drugs against several diseases.

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Congrats to the telomere/ribosome Nobelists

Congratulations to Elizabeth Blackburn, Carol Greider and Jack Szostak for the 2009 Nobel Prize in medicine. The award is for their work on telomeres, the protective caps on the ends of chromosomes that shorten with every cell division and need specialized enzymes to be replenished.

Greider, Blackburn and Szostak discovered telomerase, the enzyme that copies the ends of chromosomes using a special RNA template. Telomerase is turned off in most human cells, but cancer cells often must reactivate it so that they can keep dividing like crazy.

The discovery of telomerase has led to new leads for potential anticancer drugs. This is a good example of the impact basic research can have on medicine, since the prize-winners were not thinking about anticancer drugs in the 1980s when they were doing their work.

Telomeres are specialized protective structures at the ends of chromosomes

Telomeres are specialized protective structures at the ends of chromosomes

The telomere trio’s work relates to several lines of research at Emory.

Immunologist Cornelia Weyand and her colleagues have shown that the telomeres of T cells are abnormally shortened in patients with rheumatoid arthritis. In effect, their cells’ chromosomes are prematurely aged. This result provides some hints on how to treat autoimmune diseases.

If blood-forming stem cells can’t keep their telomeres in shape, they can’t continue to regenerate the blood. Pathologist Hinh Ly’s research has made a connection between genetic defects in telomere maintenance and bone marrow failure syndrome in human patients.

Geneticists Christa Martin and David Ledbetter have been probing the relationship between mutations or recombination in the regions of the chromosome adjacent to telomeres and developmental disorders such as autism and mental retardation.

The 2009 Nobel Prize in Chemistry, awarded to Venki Ramakrishnan, Tom Steitz and Ada Yonath, has an even stronger connection to Emory. Christine Dunham, part of a growing contingent of crystallographers here, worked on ribosome structure in Ramakrishnan’s lab at the MRC.

The ribosome is a machine that decodes mRNA and produces protein step by step

The ribosome is a machine that decodes mRNA and produces protein step by step

She is examining the molecular details of how antibiotics and viruses perturb ribosome function.

What the two Nobels have in common is that they both honor work on molecular machines containing RNA, connections to the ancient, shadowy “RNA world“.

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