A long-delayed paper on the connection between chronic fatigue syndrome and XMRV (xenotropic murine leukemia virus-related virus) finally surfaced last week in PNAS. Astute readers may recall that XMRV has also been linked to prostate cancer.
Detecting XMRV in prostate tissue. A variety of assays (neutralizing antibodies, polymerase chain reaction or fluorescence in situ hybridization) may be used to look for XMRV
The twist from last week’s paper is that the NIH/FDA team, led by Harvey Alter, didn’t find viruses all with the same sequence in chronic fatigue patients. Instead, they found a cluster of closely related, but different, viruses. While confusing, these results may explain why tests for the presence of the virus that are based on viral DNA sequences may have generated varying (and conflicting) results. An alternative assay based on antibodies, such as the one urologist John Petros and colleagues at Emory developed, may be useful because it casts a wider net.
In a collaboration with Ila Singh at the University of Utah, antiviral drug expert Raymond Schinazi has found that a number of drugs active against HIV also stop XMRV. This offers some hope that if doctors can detect members of the XMRV family, and figure out what they’re up to, they might be able to combat the troublemakers as well.
Kukar’s willingness to take on this challenge indicates that he shouldn’t have too much trouble adjusting to Atlanta’s climate. He comes to Emory from the Mayo Clinic in Jacksonville. There, he investigated potential drugs that could change how the body produces and processes beta-amyloid, a toxic protein fragment that builds up in the brains of people with Alzheimer’s.
In a paper recently published in Journal of Neuroscience, a team led by cell biologist Gary Bassell shows that PI3 kinase inhibitors could restore normal appearance and levels of protein production at the synapses of hippocampal neurons from fragile X model mice. The next steps, studies in animals, are underway.
â€œThis is an important first step toward having a new therapeutic strategy for fragile X syndrome that treats the underlying molecular defect, and it may be more broadly applicable to other forms of autism,â€ he says.
This year’sÂ Emory’s Summer Undergraduate Research Experience program is the largest it has ever been. Thursday’s poster session at the Dobbs University Center was split into two shifts so that all 99 participants could have a chance to explain their research. Graduate students in Emory’s Division of Biological and Biomedical Sciences circulated through the crowd, taking notes in order to judge the posters. The majority of participating students worked in biomedical research labs in the Woodruff Health Sciences Center.
Oxford College chemistry major Ashley Hodges explains her work on new potential anti-cancer agents to radiologist Hui Mao
SURE, organized by Emory’s Center for Science Education,Â is a ten-week program, attracting undergraduates not only from Emory but from other Atlanta-area universities and around the world.
Participants receive a stipend and on-campus housing, and have weekly meetings on ethics, research careers and lab life. About a third of former participants complete a graduate degree, according to follow-up surveys recently published in the journal Life Sciences Education. The main funding comes from Howard Hughes Medical Institute, with additional support from the National Science Foundation, National Institutes of Health and a variety of non-profit foundations.
How you vaccinate helps determine how you protect. This idea lies behind many researchers’ interest in mucosal vaccines. How a vaccine is administered (orally/nasally vs intramuscular, for example) could make a difference later, when the immune system faces the bad guys the vaccine is supposed to strengthen defenses against.
How does the route of immunization affect the quality of immunity later on? For example, is a nasal spray best when trying to prevent respiratory infections?
Memory T cells are a key part of a response to a vaccine, because they stick around after an infection, enabling the immune system to fight an invading virus more quickly and strongly the second time around. In the paper, the Emory team compared memory T cells that form in mice after they are infected in the respiratory system by a flu virus or throughout their bodies by a virus that causes meningitis (lymphocytic choriomeningitis virus or LCMV).
The authors engineered a flu virus to carry a tiny bit of LCMV (an epitope, in immunological terms) so that they could compare apples to apples by measuring the same kind of T cells. They found that memory T cells generated after a flu infection are weaker, in that they proliferate and stimulate other immune cells less, than after a LCMV infection. This goes against the idea that after a respiratory infection, the immune system will be better able to face a challenge in the respiratory system.
DNA usually occupies a privileged place inside the cell. Although cells in our body die all the time, an orderly process of disassembly (programmed cell death or apoptosis) generally keeps cellular DNA from leaking all over the place. DNA’s presence outside the cell means something is wrong: tissue injury has occurred and cells are undergoing necrosis.
Researchers from the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University have devised a way to exploit the properties of extracellular DNA to create an imaging agent for injured tissue. Niren Murthy and Mike Davis recently published a paper in Organic Letters describing the creation of â€œHoechst-IR.â€ This imaging agent essentially consists of the DNA-binding compound Hoechst 33258 (often used to stain cells before microscopy), attached to a dye that is visible in the near-infrared range. A water-loving polymer chain between the two keeps the new molecule from crossing cell membranes and binding DNA inside the cell.
Itâ€™s not a silly question, when one sees how oxidative stress and reactive oxygen species have been implicated in so many diseases, ranging from hypertension and atherosclerosis to neurodegenerative disorders. Yet large-scale clinical trials supplementing participantsâ€™ diets with antioxidants have showed little benefit.
Emory University School of Medicine scientists have arrived at an essential insight: the cell isnâ€™t a tiny bucket with all the constituent chemicals sloshing around. To modulate reactive oxygen species effectively, an antioxidant needs to be targeted to the right place in the cell.
Sergei Dikalov and colleagues in the Division of Cardiology have a paper in the July 9 issue ofÂ Circulation Research, describing how targeting antioxidant molecules to mitochondria dramatically increases their effectiveness in tamping down hypertension.
Mitochondria are usually described as miniature power plants, but in the cells that line blood vessels, they have the potential to act as amplifiers. The authors describe a â€œvicious cycleâ€ of feedback between the cellular enzyme NADPH oxidase, which produces the reactive form of oxygen called superoxide, and the mitochondria, which can also make superoxide as a byproduct of their energy-producing function.
Emory geneticist Peng Jin and his colleagues have a review in the June 25, 2010 issue ofÂ Chemistry and Biology exploring whether microRNAs offer new possibilities for pharmacology.
MicroRNAs directly regulate other genes
The microRNA pathway represents both a way for scientists to “knock down” the activity of just one gene in the laboratory, and a major way for cells to regulate their genes during development.
MicroRNAs add a big wallop of complexity on top of the standard model of molecular biology, where the information in DNA is made into RNA, and RNAs make proteins. MicroRNAs don’t get turned into protein, but directly regulate other genes.
Andrew Fire and Craig Mello received the 2006 Nobel Prize in Medicine for their discovery that short pieces of RNA, when introduced into cells, can silence genes. This “RNA interference” tactic hijacks the natural machinery inside the cell that microRNAs use.
In 2008, Jin and coworkers published in Nature Biotechnology their discovery that certain antibiotics called fluoroquinolones (ciprofloxacin is one) can make the RNA interference process work more efficiently — in general. In the review, Jin notes that scientists are starting to look for drugs that act more selectively, disrupting or enhancing a particular microRNA rather than many at once:
Since miRNAs play major roles in nearly every cellular process, the identification and characterization of small-molecule modulators of the RNAi/miRNA pathway will yield fresh insights into fundamental mechanisms behind human disease… Moreover, these RNAi modulators, particularly RNAi enhancers, could potentially facilitate the development of RNA interference as a tool for biomedical research and therapeutic interventions.
Last year, when the H1N1 flu epidemic was a major public health concern, a relatively low proportion of individuals getting sick were elderly, compared to previous flu epidemics. To explain this, scientists hypothesized that flu strains that circulated decades ago were similar enough to the novel swine-origin H1N1 strain toÂ provide some immune protection.
A universal flu vaccine would eliminate the guesswork associated with the yearly flu shot
Now, researchers at Emory’s Influenza Pathogenesis & Immunology Research Center have directly tested that hypothesis in mice, and it holds up. Exposure of mice to flu strains that circulated in 1947 or 1934 induced “robust cross-protective immune responses” and can protect them against a lethal challenge with 2009 H1N1 virus, they report in Journal of Immunology.
Ioanna Skountzou and Dimitrios Koutsananos are co-first authors of the paper.
The Emory team, led by Joshy Jacob, also reports that antibodies produced in response to the 2009 H1N1 flu strain exhibit broad cross-reactivity — they react with other H1N1 strains as well as against H3N2 flu strains. They write:
The fact that the 2009 H1N1 virus can induce such cross-reactive Abs raises the intriguing possibility that viruses such as A/California/04/2009 can be used for vaccines to induce broadly cross-reactive humoral immune responses against influenza viruses. Identifying the mechanism behind this broad reactivity may enable us to design broadly cross-reactive universal influenza vaccines.
National Institute of Allergy and Infectious Diseases director Tony Fauci, when he was at Emory for the H1N1 flu conference in April, discussed the idea of a universal flu vaccine:
Kathy Griendling, PhD (in green), surrounded by members of her lab
On June 15, 2010, vascular biologist Kathy Griendling delivered the 2010 Dean’s Distinguished Faculty lecture at Emory University School of Medicine.
Some of Griendling’s publications have been cited thousands of times by fellow scientists around the world, making her the lead member of a small group of researchers at Emory called theÂ “Millipub Club.”
With her five children and one grandson watching in the back row, Griendling explained how she and her colleagues, over the course of more than two decades at Emory, have gradually revealed the functions of a family of enzymes called NADPH oxidases in vascular smooth muscle cells. Read more