As a volunteer physician in a small hospital in Nigeria 30 years ago, I was bitten by lots of mosquitoes and soon came down with headache, chills, fever, and muscle aches. It was malaria. Fortunately, the drug available to me then was effective, but I was pretty sick for a few days. Since that time, malarial drug resistance has become steadily more widespread. In fact, the treatment that cured me would be of little use today. Combination drug therapies including artemisinin have been introduced to take the place of the older drugs , but experts are concerned the mosquito-borne parasites that cause malaria are showing signs of drug resistance again.
So, researchers have been searching the genome of Plasmodium falciparum, the most-lethal species of the malaria parasite, for potentially better targets for drug or vaccine development. You wouldn’t think such work would be too tough because the genome of P. falciparum was sequenced more than 15 years ago . Yet it’s proven to be a major challenge because the genetic blueprint of this protozoan parasite has an unusual bias towards two nucleotides (adenine and thymine), which makes it difficult to use standard research tools to study the functions of its genes.
Now, using a creative new spin on an old technique, an NIH-funded research team has solved this difficult problem and, for the first time, completely characterized the genes in the P. falciparum genome . Their work identified 2,680 genes essential to P. falciparum’s growth and survival in red blood cells, where it does the most damage in humans. This gene list will serve as an important guide in the years ahead as researchers seek to identify the equivalent of a malarial Achilles heel, and use that to develop new and better ways to fight this deadly tropical disease.
Posted In: News
Tags: adenine, antimalarial drugs, drug development, drug resistance, essential genes, genomics, global health, jumping genes, malaria, mosquito, mosquito-borne illnesses, multi-drug resistance, neglected diseases, Nigeria, P. falciparum, P. falciparum mutants, parasite, Plasmodium, Plasmodium falciparum, thymine, transposons, tropical diseases, World Health Assembly
The stars are out and shining this holiday season. But there are some star-shaped structures now under study in the lab that also give us plenty of reason for hope. One of them is a tiny virus called bacteriophage phi-6, which researchers are studying in an effort to combat a similar, but more-complex, group of viruses that can cause life-threatening dehydration in young children.
Thanks to a breakthrough technology called cryo-electron microscopy (cryo-EM), NIH researchers recently captured, at near atomic-level of detail, the 3D structure of this immature bacteriophage phi-6 particle in the process of replication. At the points of its “star,” key proteins (red) are positioned to transport clipped, single-stranded segments of the virus’ own genetic information into its newly made shell, or procapsid (blue). Once inside the procapsid, an enzyme (purple) will copy the segments to make the genetic information double-stranded, while another protein (yellow) will help package them. As the procapsid matures, it undergoes dramatic structural changes.
Tags: bacteriophage, bacteriophage phi-6, cryo-electron microscopy, cryo-EM, double-stranded RNA viruses, gastrointestinal disease, global health, imaging, procapsid, rotavirus, rotavirus vaccine, virus
There are new reports of an outbreak of Ebola virus disease in the Democratic Republic of Congo. This news comes just two years after international control efforts eventually contained an Ebola outbreak in West Africa, though before control was achieved, more than 11,000 people died—the largest known Ebola outbreak in human history . While considerable progress continues to be made in understanding the infection and preparing for new outbreaks, many questions remain about why some people die from Ebola and others survive.
Now, some answers are beginning to emerge thanks to a new detailed analysis of the immune responses of a unique Ebola survivor, a 34-year-old American health-care worker who was critically ill and cared for at the NIH Special Clinical Studies Unit in 2015 . The NIH-led team used the patient’s blood samples, which were drawn every day, to measure the number of viral particles and monitor how his immune system reacted over the course of his Ebola infection, from early symptoms through multiple organ failures and, ultimately, his recovery.
The researchers identified unexpectedly large shifts in immune responses that preceded observable improvements in the patient’s symptoms. The researchers say that, through further study and close monitoring of such shifts, health care workers may be able to develop more effective ways to care for Ebola patients.
Tags: adaptive immune system, Africa, blood, Congo, critical care, Ebola, Ebola epidemic, Ebola treatment, Ebola Virus Disease, global health, hemorrhagic fever, immunity, immunology, infectious disease, innate immunity, NIH Clinical Center, organ failure, pandemic, Sierra Leone, virology, West Africa
About a year ago, Tom Glover began sifting through a stack of applications from prospective students hoping to be admitted into the Master’s Degree Program in Human Genetics at the University of Michigan, Ann Arbor. Glover, the program’s director, got about halfway through the stack when he noticed applications from two physicians in West Africa: Charlotte Osafo from Ghana, and Yemi Raji from Nigeria. Both were kidney specialists in their 40s, and neither had formal training in genomics or molecular biology, which are normally requirements for entry into the program.
Glover’s first instinct was to disregard the applications. But he noticed the doctors were affiliated with the Human Heredity and Health in Africa (H3Africa) Initiative, which is co-supported by the Wellcome Trust and the National Institutes of Health Common Fund, and aims in part to build the expertise to carry out genomics research across the continent of Africa. (I am proud to have had a personal hand in the initial steps that led to the founding of H3Africa.) Glover held onto the two applications and, after much internal discussion, Osafo and Raji were admitted to the Master’s Program. But there were important stipulations: they had to arrive early to undergo “boot camp” in genomics and molecular biology and also extend their coursework over an extra term.
Tags: Africa, chronic kidney disease, genomics, global health, H3Africa, human genetics, Human Heredity and Health in Africa Initiative, kidneys, molecular biology, nephrology, research training, sub-Saharan Africa, West Africa
In the early 1960s, reports began to surface that some children living in remote villages in East Africa were suffering mysterious episodes of “head nodding.” The condition, now named nodding syndrome, is recognized as a rare and devastating form of epilepsy. There were hints that the syndrome might be caused by a parasitic worm called Onchocerca volvulus, which is transmitted through the bites of blackflies. But no one had been able to tie the parasitic infection directly to the nodding heads.
Now, NIH researchers and their international colleagues think they’ve found the missing link. The human immune system turns out to be a central player. After analyzing blood and cerebrospinal fluid of kids with nodding syndrome, they detected a particular antibody at unusually high levels . Further studies suggest the immune system ramps up production of that antibody to fight off the parasite. The trouble is those antibodies also react against a protein in healthy brain tissue, apparently leading to progressive cognitive dysfunction, neurological deterioration, head nodding, and potentially life-threatening seizures.
The findings, published in Science Translational Medicine, have important implications for the treatment and prevention of not only nodding syndrome, but perhaps other autoimmune-related forms of epilepsy. As people in the United States and around the globe today observe the 10th anniversary of international Rare Disease Day, this work provides yet another example of how rare disease research can shed light on more common diseases and fundamental aspects of human biology.
Tags: Africa, antibody, autoimmune disease, autoimmunity, childhood infectious diseases, cognitive dysfunction, epilepsy, global health, immunity, infectious disease, ivermectin, leiomodin-1, neglected tropical diseases, neurons, Nodding Syndrome, Onchocerca volvulus, Onchocerciasis, parasite, parasitic worm, rare disease, Rare Disease Day, River Blindness, seizures, South Sudan, Tanzania, Uganda, worm