Vulnerability to stress - Tet by Tet

Transition states like 5-hydroxymethylcytosine aren't really a new letter of the genetic alphabet – they’ve been there all along. We just didn’t see them Read more

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

Uncategorized

Cellular response to stress: autophagy

Update: Yoshinori Ohsumi’s 2016 Nobel Prize was for the study of autophagy. Hepatologist Mark Czaja, who came to Emory in 2015, is well known for his work on autophagy in the liver.

Feeling hungry? For this month’s Current Concept feature, lets take a look at the term autophagy. Taken literally, its Greek roots mean “self-digestion”.

Autophagy in mouse liver cells — the autophagic vesicles are green (Image from PNAS)

Autophagy is a basic response of cells to not having enough nutrients or other forms of stress: they begin to break down parts of the cell that are broken or not needed. The term autophagy was coined by Belgian biochemist Christian de Duve in the 1960s. He discovered lysosomes, the parts of the cell where breakdown can take place.

Autophagy comes up in many contexts in biomedical research. Indeed, there is an entire scientific journal devoted to the topic. At Emory, researchers interested in cancer, Parkinson’s, stroke and liver disease all have touched upon the process of autophagy.  Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

How beneficial bacteria talk to intestinal cells

Guest post from Courtney St Clair Ardita, MMG graduate student and co-author of the paper described. Happy Halloween!

In the past, reactive oxygen species were viewed as harmful byproducts of breathing oxygen, something that aerobic organisms just have to cope with to survive. Not any more. Scientists have been finding situations in humans and animals where cells create reactive oxygen species (ROS) as signals that play important parts in keeping the body healthy.

One example is when commensal or good bacteria in the gut cause the cells that line the inside of the intestines to produce ROS. Here, ROS production helps repair wounds in the intestinal lining and keeps the environment in the gut healthy. This phenomenon is not unique to human intestines. It occurs in organisms as primitive as fruit flies and nematodes, so it could be an evolutionarily ancient response. Examples of deliberately created and beneficial ROS can also be found in plants, sea urchins and amoebas.

Researchers led by Emory pathologist Andrew Neish have taken these findings a step further and identified the cellular components responsible for producing ROS upon encountering bacteria. Postdoctoral fellow Rheinallt Jones is first author on the paper that was recently published in The EMBO Journal. Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Visualizing retrograde flow

This month’s intriguing image is a set of videos produced by cell biologist James Zheng’s laboratory. Looking at this video of a cell can be mesmerizing. The edges of the cell appear to be flowing inward, like a waterfall. Zheng explains that this is a phenomenon called “actin retrograde flow.”

Actin is a very abundant protein found in animals, plants and fungi that forms filaments, making up the cell’s internal skeleton. What we are seeing with retrograde flow is that molecules of actin are being added to one end of the filaments while coming loose from the other end.Actin

Zheng’s laboratory is studying a protein called cofilin, which disassembles actin filaments. Using a technique called CALI (chromophore-assisted laser inactivation) the scientists http://www.troakley.com/ used a laser to blast cofilin, inactivating it. This is why, partway through the loop, after the word CALI appears, the flow slows down. Postdoctoral fellow Eric Vitriol is the lead author on a paper in Molecular Biology of the Cell that includes these videos.

Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Gene duplication leads to obesity in childhood syndrome

A team of researchers has discovered a genetic syndrome that causes childhood obesity, intellectual disability and seizures. The syndrome comes from an “unbalanced” chromosomal translocation: affected individuals have additional copies of genes from one chromosome and fewer copies of genes from another.

The results were published this week in Proceedings of the National Academy of Sciences, Early Edition.

Katie Rudd, PhD, assistant professor of human http://www.raybanoutletes.com/ genetics at Emory University School of Medicine, is senior author of the paper. Research specialist Ian Goldlust, now a graduate student in the NIH-Oxford-Cambridge Scholars Program, is the first author. Co-authors include investigators from around the USA and Australia.

Rudd’s team was able to connect the contribution of one gene, GNB3, among many involved in the translocation, to the obesity aspect of the syndrome. Her lab created a mouse model with an extra copy of the GNB3 gene and found that the mice are obese. The mice are on average 6 percent (males) or 10 percent (females) heavier.

Rudd says her work was greatly assisted by collaboration with the Unique Rare Chromosome Disorder Support Group, a UK-based charity. Within Unique, a few parents had together found that their children had translocations involving the same chromosomes and similar symptoms. They contacted Rudd and helped her find additional affected families. Her study includes seven unrelated patients.

“It really was a group effort, and Unique was the linchpin,” she says. “Managing to find seven families with exactly the same rare translocation would have been extremely difficult otherwise.”

Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Exception from informed consent: what patients say

Informed consent is a basic principle of clinical research. Doctors are required to make sure that patients understand what’s involved with experimental treatments, and patients should only participate if they provide consent.

However, an important area of clinical research takes place outside of this general rule, because some life-threatening conditions – seizures, traumatic brain injury and cardiac arrest, as examples — make it impossible for the patient to learn about a clinical trial and make a decision about whether to participate. The urgency of treatment can also mean that seeking proxy consent from a relative is impractical.

A recent editorial in USA Today highlights this area of research, called EFIC (exception from informed consent). The author, Katherine Chretien from George Washington University, cites research from Emory investigators Neal Dickert and Rebecca Pentz.

Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

The creeping edges of cells: lamellipodia

Lamellipodia with red box
This month’s Image feature highlights lamellipodia, the thin sheet-like regions at the leading edges of migrating cells. Lamellipodia act as tiny creeping motors that pull the cell forward.

To help visualize lamellipodia, Adriana Simionescu-Bankston, a graduate student in Grace Pavlath’s lab, provided us with this photo of muscle cells. The red box shows an example of lamellipodia. Notice the edge of the cell, where the green color is more intense.

The green color comes from FITC-phalloidin, which stains F-actin, the Ray Ban outlet filaments that make up a large part of the cells’ internal skeleton. (Phalloidin is an actin-binding toxin originally isolated from death cap mushrooms, and FITC is what makes it green.) The blue color comes from DAPI, a dye that stains the DNA in the nucleus.

Simionescu-Bankston and Pavlath recently published a paper in the journal Developmental Biology, examining the function of a protein called Bin3 in muscle development and regeneration. They found that Bin3 appears to regulate lamellipodia formation; in mice that lack Bin3, muscle cells have fewer lamellipodia and the muscle tissues regenerate slower after injury. Bin3 is also important in the eye, since the “knockout” mice develop cataracts soon after birth.

 

Posted on by Quinn Eastman in Uncategorized Leave a comment

From the genetic code to new antibiotics

Biochemist Christine Dunham and her colleagues have a new paper in PNAS illuminating a long-standing puzzle concerning ribosomes, the factories inside cells that produce proteins.

Ribosomes are where the genetic code “happens,” because they are the workshops where messenger RNA is read out and proteins are assembled piece by piece. As a postdoc, Dunham contributed to Nobel Prize-winning work determining the molecular structure of the ribosome with mentor Venki Ramakrishnan.

Ribosomes are the workshops for protein synthesis and the targets of several antibiotics

The puzzle is this: how messenger RNA can be faithfully and precisely translated, when the interactions that hold RNA base pairs (A-U and G-C) together are not strong enough. There is enough “wobble” in RNA base pairing such that transfer RNAs that don’t match all three letters on the messenger RNA can still fit.

Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Supreme decision on DNA patents

In these days of political polarization, how often does the United States Supreme Court make a unanimous decision? When the case has to do with human genes and their patentability!

The case concerned patents held by Utah firm Myriad Genetics on the BRCA1 and 2 genes. Mutations in those genes confer an increased risk of breast and ovarian cancer. The patents in dispute claimed the genes themselves rather than just the technology for reading them.

Cecelia Bellcross, director of Emory’s genetics counseling program and an expert on breast cancer genetics counseling, reports that “in general, the clinical genetics community is jumping up and down, as are a lot of genetics lab directors and definitely patient advocacy groups.”

Myriad’s BRCA tests cost more than $3,000. Several competing firms announced that they would offer tests for the BRCA1 and 2 mutations at significantly lower prices.

Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

An indicator of aberrant stem cell reprogramming

The 2012 Nobel Prize in Medicine was awarded to Shinya Yamanaka and John Gurdon for the discovery that differentiated cells in the body can be reprogrammed. This finding led to the development of “induced pluripotent stem cells.”

These cells were once skin or blood cells. Through a process of artificial reprogramming in the lab, scientists wipe these cells’ slates clean and return them to a state very similar to that of embryonic stem cells. But not exactly the same.

It has become clear that iPS cells can retain some memories of their previous state. This can make it easier to change an iPS cell that used to be a blood cell (for example) back into a blood cell, compared to turning it into another type of cell. The finding raised questions about iPS cells’ stability and whether http://www.troakley.com/ iPS cell generation – still a relatively new technique – would need some revamping for eventual clinical use.

Hotspots where iPS cells differ from ES cells

Chromosomal hotspots where iPS cells differ from ES cells

It turns out that iPS cells and embryonic stem cells have differing patterns of methylation, a modification of DNA that can alter how genes behave even if the underlying DNA sequence remains the same. Some of these differences are the same in all iPS cells and some are unique for each batch of reprogrammed cells.

Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Alphabet of modified DNA keeps expanding

Move over, A, G, C and T. The alphabet of epigenetic DNA modifications keeps getting longer.

A year ago, we described research on previously unseen information in the genetic code using this metaphor:

Imagine reading an entire book, but then realizing that your glasses did not allow you to distinguish “g” from “q.” What details did you miss?

Geneticists faced a similar problem with the recent discovery of a “sixth nucleotide” in the DNA alphabet. Two modifications of cytosine, one of the four bases http://www.raybani.com/ that make up DNA, look almost the same but mean different things. But scientists lacked a way of reading DNA, letter by letter, and detecting precisely where these modifications are found in particular tissues or cell types.

Now, a team… has developed and tested a technique to accomplish this task.

Well, Emory geneticist Peng Jin and his collaborator Chuan He at the University of Chicago are at it again.

Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment