Congratulations to Richard Compans, PhD, who delivered the Dean’s Distinguished Faculty Lecture on May 12, joining a select group of Emory researchers who have received this award. After Dean Chris Larsen presented the award, Compans also received a Catalyst award from the Georgia Research Alliance, presented by GRA President and CEO Mike Cassidy.
At Emory, Compans has led research on ways to improve influenza vaccination, such as vaccines based on non-infectious virus-like particles and microneedle patches for delivery (now being tested clinically). The 2009 H1N1 flu epidemic, as well as concern about pandemic avian flu, have meant that Compans’ work has received considerable attention in the last several years. In his talk, he also discussed his early work on the structure of influenza virus, the virus’s complex ecology, and the limitations of current flu vaccines.
Compans was recruited to Emory from UAB in 1992 and was chair of Emory’s microbiology and immunology department for more than a decade. He was also instrumental in recruiting Rafi Ahmed to establish and lead the Emory Vaccine Center. He is now co-principal investigator of the Emory-UGA Center of Excellence for Influenza Research and Surveillance.
Some recent papers that illustrate the extent of Compans’ influence: Read more
Third in a series on malaria immunology from graduate student Taryn McLaughlin. Sorry for the delay last week, caused by technical blog glitches.
It’s easy for me to find reasons to brag when it comes to research here at Emory. However, even an unbiased person should be excited about the malaria vaccine platform being developed by Alberto Moreno at the Emory Vaccine Center.
His vaccine is based on a chimeric protein (a protein that is a combination of bits and pieces of multiple proteins, a la the creature from Greek mythology) that should get your immune system to target multiple stages of the Plasmodium vivax life cycle. Part of it targets the infectious sporozoite, part of it targets the blood stage merozoite, and part of it will even target the transmitted gamete in future versions. This seems like a no brainer. Of course we should be targeting multiple stages!
Continuing from Monday’s post, IMP graduate student Taryn McLaughlin explains why the most advanced malaria vaccine is actually not that great.
Malaria has plagued humans for thousands of years. And while we have known the causative agents of the disease- for 150 years, malaria remains scientifically frustrating. In fact, one of the most common treatments for the disease is simply a derivative of a treatment used in ancient China.
One of the most frustrating features is that there is no sterilizing immunity. In other words, for many diseases once you are infected with the microbe responsible, you develop an immune response and then never get the disease again. Not so with malaria. Compounded with terrible treatment and the impracticality of ridding the world of mosquitos, a vaccine sounds like pretty much our only hope. And yet this has been scientifically challenging and unsuccessful for many many reasons.
In fact a number of vaccine candidates have come along in the last few decades that have seemed SO promising only to go on and break our hearts in clinical trials. The most recent of which is a vaccine that goes by the name RTS,S (named for the different components of the vaccine).
As a quick refresher, Plasmodium enters the body via mosquitos as a sporozoite. It then migrates through the skin going into the blood and eventually making itâ€™s way to the liver. Here it goes inside liver cells where it replicates and turns into merozoites (such that one sporozoite becomes thousands of merozoites). This stage of the disease is asymptomatic. Some time later, all those merozoites burst out of your liver cells causing mayhem and invading your red blood cells. Here, they once again replicate and metamorphose. Fun times. Anyways, during the last stage, some of those plasmodium become gametes which get eaten by mosquitos thus completing the life cycle. Read more
In recognition of World Malaria Day, Lab Land will have a series ofÂ posts from Taryn McLaughlin, a graduate student in Emoryâ€™s IMP program. Her posts will set the stage for upcoming news about malaria research at Emory and Yerkes. Taryn is part of Cheryl Dayâ€™s lab and is also an associate producer with theÂ AudiSci podcast.
Those of us in the US are fortunate to not have to consider malaria in our day-to-day lives. Globally though, malaria is a serious public health threat with nearly 3.2 billion people at risk and close to half a million deaths every year. The scientific community has been developing malaria vaccines for decades. Yet a robust vaccine still remains elusive. Why?
IMP graduate student Taryn McLaughlin
One set of barriers comes from economics:Â malariaâ€™s strongest impact is in developing countries. But there is just as strong a case to be made for scientific obstacles. Frankly, the parasite (technically a bunch of species of microbes that I’ll just lump together under the umbrella term Plasmodium) that causes malaria is just smarter than we are.
I’m only kidding, but it is a fascinating organism. Its complexity makes it difficult to pin down and also interesting to write about. But before we talk about why Plasmodium is such a pain, let’s first discuss what exactly makes an effective vaccine. Read more
Emory’s Alzheimer’s Disease Research Center recently announced a grant that will support studies on the connections between blood pressure regulation and Alzheimer’s disease. It focuses on the roles of the renin-angiotensin system, the targets of common blood pressure medications, and endothelial cells, which line blood vessels.
Research on that theme is already underway at Emory. Malu Tansey is leading a large project funded by the National Institute on Aging ($3.4 million) with a similar title: “Inflammation and Renin-Angiotensin System Dysfunction as Risk Factors for Alzheimer’s Disease.” Co-investigators are Felicia Goldstein and Lary Walker at Emory and Christopher Norris at the University of Kentucky.
Both studies build on evidence that molecules that control blood pressure and inflammation also drive progression of Alzheimer’s disease, including work by Emory’s Whitney Wharton and Ihab Hajjar. They had found in an observational study that people who take medications targeting the renin-angiotensin system have a lower risk of progressing from mild cognitive impairment to Alzheimer’s.
Wharton is gearing up to test that idea more directly in an interventional study with the generic angiotensin receptor blocker telmisartan. This study is part of a Part the Cloud initiative supported by the Alzheimer’s Association.
Tansey’s project has started bearing fruit in an animal model of Alzheimer’s, according to this Keystone meeting report from Alzforum. Last summer, her graduate student Kathryn Macpherson described initial findings on the effects of an anti-inflammatory (anti-TNF) agent, which also has positive effects in a Parkinson’s model, and her plans to investigate the effects of high-sugar, high-fat diet.
How should doctors measure how messed up someoneâ€™s intestinal microbiome is?
This is the topic of a recent paper in American Journal of Infection Control from Colleen Kraft and colleagues from Emory and the Centers for Disease Control and Prevention. The corresponding author is epidemiologist Alison Laufer Halpin at the CDC.
A â€œmicrobiome disruption indexâ€ could inform decisions on antibiotic stewardship, where a patient should be treated or interventions such as fecal microbial transplant (link to 2014 Emory Medicine article) or oral probiotic capsules.
What the authors are moving towards is similar to Shannonâ€™s index, which ecologists use to measure diversity of species. Another way to think about it is like the Gini coefficient, a measure of economic inequality in a country. If there are many kinds of bacteria living in someoneâ€™s body, the disruption index should be low. If there is just one dominant type of bacteria, the disruption index should be high.
In the paper, the authors examined samples from eight patients in a long-term acute care hospital (Wesley Woods) who had recently developed diarrhea. Using DNA sequencing, they determined what types of bacteria were present in patients’ stool. The patientsâ€™ samples were compared with those from two fecal microbial transplant donors. Read more
Intestinal inflammation in mice can be dampened by giving them a diet restricted in amino acids, the building blocks of proteins, researchers have found. The results were published online by Nature on Wednesday, MarchÂ 16.
The findings highlight an ancient connection between nutrient availability and control of inflammation. They also suggest that a low protein diet — or drugs that mimic its effects on immune cells — could be tools for the treatment of inflammatory bowel diseases, such as Crohnâ€™s disease or ulcerative colitis.
The research team, led by Emory Vaccine Center immunologist Bali Pulendran, discovered that mice lacking the amino acid sensor GCN2 are more sensitive to the chemical irritant DSS (dextran sodium sulfate), often used to model colitis in animals. This line of research grew out of the discovery by Pulendran and colleagues that GCN2 is pivotal for induction of immunity to the yellow fever vaccine.
â€œIt is well known that the immune system can detect and respond to pathogens, but these results highlight its capacity to sense and adapt to environmental changes, such as nutritional starvation, which cause cellular stress,â€ he says.
A recent WABE â€œCloser Lookâ€ interview with Mark Mulligan, executive director of the Emory Vaccine Centerâ€™s Hope Clinic, covers a lot of ground. It starts off with a segment — also aired on Marketplace — from reporter Michell Eloy, who visited the Hope Clinicâ€™s lab. We hear a machine processing blood samples from a study testing an experimental Ebola vaccine and a roundup of Ebola vaccine developments.
We also hear from Carl Davis, postdoc in Rafi Ahmedâ€™s lab, who is part of the DARPA-funded team research project studying the utility of antibodies from Ebola survivors. [Other recent news on this topic from The Scientist.]
Then, reporters Rose Scott and Jim Burress discuss several different Ebola vaccines with Mulligan. One is based on chimpanzee adenovirus, was tested at the Hope Clinic and elsewhere in the USA and the UK, and then in Liberia. While this vaccine was safe and it appears to stimulate the immune system appropriately, the outbreak fizzled out (a good thing!) before it was possible to tell if the vaccine protected people from Ebola infection. Read more
In injured mouse intestines, specific types of bacteria step forward to promote healing, Emory scientists have found.Â One oxygen-shy type of bacteria that grows in the wound-healing environment,Â Akkermansia muciniphila, has already attracted attention for its relative scarcity in both animal andÂ human obesity.
An intestinal wound brings bacteria (red) into contact with epithelial cells (green). The bacteria can provide signals that promote healing, if they are the right kind.
The findings emphasize how the intestinal microbiome changes locally in response to injury and even helps repair breaches. The researchers suggest that some of these microbes could be exploited as treatments for conditions such as inflammatory bowel disease.
The results were published on January 27 inÂ Nature Microbiology.Â Researchers took samples of DNA from the colon tissue of mice after they underwent colon biopsies. They used DNA sequencing to determine what types of bacteria were present.
â€œThis is a situation resembling recovery after a forest fire,â€ says Andrew Neish, MD, professor of pathology and laboratory medicine at Emory University School of Medicine. â€œOnce the trees are gone, there is an orderly succession of grasses and shrubs, before the reconstitution of the mature forest. Similarly, in the damaged gut, we see that certain kinds of bacteria bloom, contribute to wound healing, and then later dissipate as the wound repairs.â€ Read more