| RESEARCH HIGHLIGHTS |
when these processes become uncoupled. These models will help understand
gastric diseases as well as normal pyloric gland development. “For instance, we can examine whether gastric cancer is the result of an imbalance between stem cell proliferation and differentiation or is
associated with a slower replacement of stem cells, meaning that faulty stem cells are not replaced early enough” says Carmen Pin, a visiting researcher from the Institute of Food Research in the UK who undertook the study with Barker and Marc Leushacke from the A*STAR team.
“The same approach could be used to
study the dynamics of any population of cells which can be genetically labeled and traced in other organs,” they added.
1. Leushacke, M., Barker, N. & Pin, C. Quantifying Lgr5-positive stem cell behaviour in the pyloric epithelium. Scientific Reports 6, 21923 (2016).
Bacterial biofilms:
A PROBE FOR BIOFILMS UNVEILS BACTERIA
The key to overcoming antibacterial resistance could lie in our ability to detect biofilms — a structure formed by bacterial communities that protects them from anti- bacterial drugs. Scientists at A*STAR have developed the first fluorescent probe to detect biofilms in a living animal model of corneal infection, allowing for access to the bacteria for treatment. Bacterial infections have traditionally been
treated using antibiotics. “When bacteria are isolated, they are relatively easy to detect and kill using antibiotics. Once they get together, however, they form a protective structure around their community — a so-called biofilm,” says Young-Tae Chang, team leader from the A*STAR Singapore Bioimaging Consortium. These biofilms — thick substances
made of extracellular DNA, proteins, polysaccharides and fatty acids — are a large contributing factor for antibiotic resistance. “It is hard for antibiotics to penetrate the biofilm to reach the bacteria and treat them,” explains Chang. To access biofilm-covered bacteria, scientists
first need to be able to detect the protective structure. Chang and his team discovered a biofilm probe using a technique previously
26 A*STAR RESEARCH eDNA Biofilm Fatty acid
Bacterial biofilms are made of proteins, extracellular DNA (eDNA), polysaccharides and fatty acids. The first biofilm probe, CDy11, developed by A*STAR researchers, binds amyloid, a major protein required for biofilm structure and function.
ISSUE 5 | OCTOBER – DECEMBER 2016
developed in his lab, called the diversity-oriented fluorescence library approach (DOFLA). DOFLA uniquely generates small fluorescent
molecules for use as probes by creating simple fluorescent scaffolds that can be modified upon binding to target molecules. DOFL compounds are generated without prior knowledge of a target, which overcomes the limitations of target-oriented approaches, where
Polysaccharide
the applicability of such compounds in complex biological systems is often not guaranteed. Chang and his team screened their 10,000-
member molecular library for compounds that bind amyloid, a major scaffolding protein in biofilm. They identified the probe, named CDy11 (compound of designation yellow 11), by screening the compounds in high- versus low-amyloid expressing strains of the
O NH CDy11 F OMe Amyloid fibre F F
THE FIRST PROBE FOR BACTERIAL BIOFILMS OPENS THE DOOR FOR NEW WAYS TO COMBAT ANTIBACTERIAL RESISTANCE
© 2016 A*STAR Singapore Bioimaging Consortium
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