| RESEARCH HIGHLIGHTS |


high consumption of animal protein, not plant protein. “Childhood obesity and metabolic diseases


have reached epidemic levels globally,” says Ling-Wei Chen, joint first author of the research paper, together with Mya-Thway Tint, both at Singapore’s Yong Loo Lin School of Medicine. He adds that Asians are at higher risk of metabolic diseases than Caucasians of similar BMI levels. The study’s focus on mothers of Asian origin therefore makes it especially relevant for planning effective dietary guidance throughout the region.


One strength of the GUSTO study is


that it can tease out differences related to different cultural backgrounds. The beneficial influence of high protein diets, for example, was stronger in Chinese and Indians than in Malays. “This may be due to inherent differences in body composition, or dietary pattern, among these groups,” says Yung Seng Lee, also of the A*STAR group. The researchers are now monitoring the


children through their early years to detect longer- term effects. They have already performed new MRI scans in the children’s


fifth year, with further scans planned between 12 and 14. “Our early results may provide invaluable information for offering better nutritional guidance to pregnant women and those planning a pregnancy, but we need to continue to track the growth of these children to confirm this” says Lee.


1. Chen, L-W., Tint, M-T., Fortier, M. V., Aris, I. M., Bernard, J. W. et al. Maternal macronutrient intake during pregnancy is associated with neonatal abdominal adiposity: The growing up in Singapore towards healthy outcomes (GUSTO) study. The Journal of Nutrition 146, 1571–1579 (2016).


Immunology:


ONE-STEP IMMUNE ACTIVATION


Monocytes have a one-step pathway for inflammasome activation.


HOW WHITE BLOOD CELLS JUMP INTO ACTION IN RESPONSE TO FOREIGN MICROBES


Pro-inflammatory molecules in the blood are essential for fighting off microbial invaders. But too much of these immune-signaling factors, and the body can go into septic shock. A team from the A*STAR Singapore Immunology Network has now elucidated the mechanism by which bacterial pathogens can rapidly trigger the processing of a key pro-inflammatory protein into its active form1. This discovery “offers new drug targets for


acute and chronic inflammatory disorders, including sepsis,” says Alessandra Mortellaro, the A*STAR immunologist who led the research. The body’s immune system reacts to


microbial infection through a group of white www.astar-research.com


blood cells that release immune-signaling molecules known as cytokines, including one called interleukin-1β (IL-1β). Yet, this cytokine occurs first in a biologically inactive form, and must be processed by caspase-1, an enzyme which itself is activated by a multi protein complex called the inflammasome. In most types of immune cells, revving


up the inflammasome requires a priming stimulus followed by a second activation signal. But in monocytes — the key mediators of early responses to infection — inflam- masome activation happens in a distinctive one-step pathway following exposure to a component of the bacterial wall, known as a


lipopolysaccharide (LPS). How this occurs, however, was poorly understood until Mortel- laro and her colleagues found out. The researchers isolated monocytes from


human blood, cultured the cells in their laboratory, and then added LPS derived from the bacterium Escherichia coli. They noticed that two enzymes, caspase-4 and -5, seemed to be expressed in the cells following LPS exposure, and this led to rapid processing of the caspase-5. Mortellaro and her team then blocked the


activity of these enzymes to show not only that caspase-4 and -5 are essential for cytokine release, but that some of the products of caspase-5 processing and other key molecular


A*STAR RESEARCH 45


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