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Archive - Nov 30, 2015

Malaria Parasite Targets Liver’s EphA2 Receptor to Launch Successful Infection; New Finding Is “Critically Important Advance” Says Chief of NIAID’s Malaria Cell Biology Section at NIH

Scientists at the Center for Infectious Disease Research (CIDR) in Seattle, Washington recently uncovered a critical piece in the puzzle of how malaria parasites infect their host. The work, published online on November 27, 2015 in Science, reveals the details of how the malaria parasite invades its initial target organ, the liver. The Science article is titled “Malaria Parasites Target the Hepatocyte Receptor EphA2 for Successful Host Infection." Without infection of the liver, the parasites cannot multiply or spread to the blood. Infection of the blood causes illness, spread of the disease, and, ultimately, death. "This discovery is significant because it reveals a vital interaction between the malaria parasite and the person it infects. Before, we knew little about that interaction. The molecular details of our discovery will facilitate the design of new drugs and new vaccines," said Alexis Kaushansky, Ph.D., an Assistant Professor at the CIDR. The discovery was made through collaborative research among the laboratories of Stefan Kappe, Ph.D., Noah Sather, Ph.D., and Alexis Kaushansky, Ph.D. The combination of cross-disciplinary, collaborative research and technological approaches has allowed this type of discovery to be possible. As Louis H. Miller, M.D., Chief of the NIAID’s Malaria Cell Biology Section at the NIH, notes, "The findings on the liver receptor EphA2 for malaria parasite sporozoite invasion of liver cells is a critically important advance and might allow us to devise new strategies to block parasite infection." Dr. Miller was not involved in the reported research. The image shows the structure of the EphA2 protein.

[Press release] [Science abstract]

Depletion of Normal BRCA1 Protein in Neurons Linked to Alzheimer’s Disease; Non-Mutated BRCA1 Required for Normal Learning & Memory; First-Ever Such Results Reported by Gladstone Institutes

Researchers from the Gladstone Institutes in San Francisco have shown, for the first time, that the unmutated BRCA1 (breast cancer 1) protein is required for normal learning and memory and is depleted by Alzheimer’s disease. BRCA1 is a key protein involved in DNA repair, and mutations that impair its function increase the risk for breast and ovarian cancer. The new study, published online today (November 30, 2015) in an open-access article in Nature Communications, demonstrates that Alzheimer’s disease is associated with a depletion of BRCA1 protein in neurons and that BRCA1 depletion can cause cognitive deficits. The article is titled ““DNA Repair Factor BRCA1 Depletion Occurs in Alzheimer Brains and Impairs Cognitive Function in Mice.” “BRCA1 has so far been studied primarily in dividing (multiplying) cells and in cancer, which is characterized by abnormal increases in cell numbers,” says first author Elsa Suberbielle, Ph.D., a research scientist at the Gladstone Institutes. “We were therefore surprised to find that it also plays important roles in neurons, which don’t divide, and in a neurodegenerative disorder [Alzheimer’s disease] that is characterized by a loss of these brain cells.” In dividing cells, BRCA1 helps repair a type of DNA damage known as double-strand breaks that can occur when cells are injured. In neurons, though, such breaks can occur even under normal circumstances in the absence of cell division, for example, after increased brain activity, as shown by the team of Gladstone scientists in an earlier study. The researchers speculated that, in brain cells, cycles of DNA damage and repair facilitate learning and memory, whereas an imbalance between damage and repair disrupts these functions. To test this idea, the scientists experimentally reduced BRCA1 levels in the neurons of mice.

Novel Technique Allows Scientists to ID Non-Coding Sequences That Regulate Expression of Seemingly Very Distant Genes; “Snap-Shot” DNA Folding Findings May Shed More Light on Autoimmune & Other Diseases

A collaboration between researchers at the Babraham Institute and at the University of Manchester, both in the UK, has mapped the physical connections occurring in the genome to shed light on the parts of the genome involved in autoimmune diseases. Using a new technique, called Capture Hi-C, the team revealed novel insights into how changes in the genetic sequence can have a biological effect and increase the risk of disease. This new work was published online on November 30, 2015, in an open-access article in Nature Communications. The article is titled “Capture Hi-C Reveals Novel Candidate Genes and Complex Long-Range Interactions with Related Autoimmune Risk Loci.” The Human Genome Project provided much of the human DNA code and large population studies have since identified DNA sequence changes that are associated with a wide range of diseases, such as cancer, cardiovascular disease, and immune system disease. Because many of these changes fall outside the parts of the genome that contain protein-coding genes, understanding the biological relevance of the genetic change was akin to the party game ‘pin the tail on the donkey’ when it came to identifying the genes that these regions associated with. Understanding these associations represents the key to uncovering the causal genetic factors of disease. The new technique developed by researchers at the Babraham Institute identified a way to “freeze-frame” the genome and capture its three-dimensional conformation where the DNA folds to bring seemingly distant regions into close contact. This “snapshot” pinpoints where non-coding regulatory regions contact the genes that they control, often over large genomic distances.

Risk-Takers Smarter, New Study Suggests; Results Are Counter to Those of Previous Studies

Do you often take chances and yet still land on your feet? Then you probably have a well-developed brain. This surprising conclusion made as part of a project studying the brains of young male high and low risk-takers. The tests were carried out at the University of Turku in Finland under the direction of SINTEF (, using both the functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) techniques to measure activation-related and structural correlates of risky behavior, respectively. The aim of the project was to investigate the decision-making processes within the brains of 34 young men aged 18 or 19. Based on psychological tests, they were divided into two groups of low and high risk-takers, respectively. "We expected to find that young men who spend time considering what they are going to do in a given risk situation would have more highly developed neural networks in their brains than those who make quick decisions and take chances," says SINTEF researcher and behavioral analyst Dagfinn Moe, Ph.D. "This has been well documented in a series of studies, but our project revealed the complete opposite," he says. The surprising results have now been published in two articles, both published in the open-access journal PLOS ONE. One article is titled “Risk-Taking Behavior in a Computerized Driving Task: Brain Activation Correlates of Decision-Making, Outcome, and Peer Influence in Male Adolescents,” and was published online on June 8, 2015. The other article is titled “Brain Structural Correlates of Risk-Taking Behavior and Effects of Peer Influence in Adolescents,” and was published online on November 12, 2014.