A Research Blog

Psychedelic cerebrum

 

A coronal section of a mouse brain is set ablaze with the fluorescent glow of different markers. Myelin in green, axons in red, microglia in magenta and nuclei in blue brings the structure of the hippocampus, striatum, thalamus and hypothalamus into focus.

 Image by Chan Jia Pei, PhD student in the laboratory of Professor David Silver
Cardiovascular and Metabolic Disorders Programme
Duke-NUS Medical School

 

Julien Pompon, molecular entomologist and Assistant Professor in the Emerging Infectious Diseases Programme at  Duke-NUS Medical School shines a light on his work with mosquitoes and what attracts and repels these pesky (but resilient) insects.

MosquitoHow do you test for behaviour in mosquitoes?

We observe mosquito behaviour primarily while they feed, which corresponds to the transmission phase. Mosquitoes are observed in real time by a researcher who rates their behaviour - such as the mosquito’s landing, insertion of the proboscis, imbibing of blood, number and time of each probe, etc. Real-time behaviour is then used to compute several important parameters that help us to assess the impact of different factors on mosquito biting success.

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Prof Michael Chee

This article was contributed by Professor Michael Chee, Director, Centre for Cognitive Neuroscience, Duke-NUS Medical School

fMRI, a brain imaging technique, can detect spontaneous fluctuations in blood flow that are synchronized across functionally related but physically separate brain regions. More recently, it has been shown that this type of functional connectivity, evaluated by when a person simply lies down in a MRI scanner with his / her eyes open, is not static. Instead, it displays recurrent shifting patterns not unlike a restless sea. Although dynamic shifts in functional connectivity have been suspected to signify changing mental states, clear proof that the shifts have behavioral significance has been elusive.

A team led by Michael Chee and Juan Zhou of Duke-NUS Medical School, Singapore and communicated in the Aug 8th issue of the Proceedings of the National Academy of Sciences (USA) found the missing link between shifting mental gears and imaging data through sophisticated analyses anchored on the everyday observation that when we are sleepy, our eyelids tend to shut.

Brain web

 

Human pluripotent stem cells (hPSCs)-induced GABAergic neurons can be seen here with the help of immunostaining. Neuronal dendrites are in red and identify neurons, while GABA positive sections in green further proves these neurons are GABAergic. These human GABAergic neurons were generated using a rapid and highly efficient single-step protocol published in Cell Reports by Duke-NUS Assistant Professor Shawn Je, National Neuroscience Institute Research Fellow Dr Alfred Sun and NUS Graduate School PhD student Mr Yuan Qiang, which can be taken advantage of to study human neuropsychiatric and neurological disorders related to GABAergic neuron dysfunction. More about their work can be read here.

Image by Yuan Qiang, NUS Graduate School PhD Student
Duke-NUS Medical School


aPKC (an apical protein in red), Mira (a basal protein in green) and DNA (in blue) were labeled in wild-type neural stem cells. (Image credit: Yingjie Zhang, Duke-NUS Medical School)

In this biobytes podcast, Duke-NUS’ very own Assoc Prof Wang Hongyan discusses her recent publication in Journal of Cell Biology that reports the role of ADP ribosylation factor like 2 (arl2) and mini spindles (msps) genes in asymmetric cell division.

Human GADD34 (Image credit Phosphositeplus, www.phosphosite.org)

Image credit: PhosphoSitePlus®, www.phosphosite.org

Name: GADD34-containing eukaryotic initiation factor 2α phosphatase (GADD34)

Action: Dephosphorylates eukaryotic initiation factor 2α (eIF2α), thereby reducing the translation of endoplasmic reticulum (ER)-targeted proteins

Gene: Ppp1r15a

What was known before:

GADD34 was thought to only be expressed as a response to cellular stress, where its main function is to reverse eIF2α phosphorylation and promote the translation of stress response proteins, so as to mitigate cellular stress and facilitate recovery.

Past and present Duke-NUS researchers recently attended the Federation of American Societies for Experimental Biology (FASEB) Conference on Protein Phosphatases in Colorado, USA. Professor David Virshup and Assistant Professor Koji Itahana from the Duke-NUS Cancer and Stem Cell Biology Programme and Professor Shirish Shenolikar from the Duke-NUS Cardiovascular and Metabolic Disorders Programme gave talks, while Duke-NUS Research Fellow Dr Lee Ha Yin snagged the best poster award. 

Dr Lee Ha Yin and Professor Catherine Pallen, (FASEB) Conference on Protein Phosphatases Chair, Professor at the University of British Columbia and former member of the Institute of Molecular and Cell Biology, A*STAR

From left to right: Dr Lee Ha Yin and Professor Catherine Pallen, (FASEB) Conference on Protein Phosphatases Chair, Professor at the University of British Columbia and former member of the Institute of Molecular and Cell Biology, A*STAR

 

Till now, transporters for DHA uptake in the eye have not been identified. Duke-NUS PhD student Bernice Wong has been able to show that the transporter Mfsd2a is found at the blood-retinal barrier (BRB) and is required for Docosahexaenoic acid (DHA) uptake in the eye – thereby proving Mfsd2a’s importance for normal eye development.Plastic sections of mice's eyes with blue staining to visualise the layers

DHA is highly enriched in the eye and is considered to be required for normal eye function. Photoreceptors are responsible for conferring vision, and its outer segments account for the highest body concentration of DHA per unit area. However, the eye does not synthesise DHA, and must import it from the blood. Like the blood-brain barrier (BBB), the eye too, has a BRB.

Bernice is the first author of this paper published in the Journal of Biological Chemistry (JBC), while its senior author is Professor David Silver, Director of Graduate Studies at Duke-NUS and the Deputy Director of the Duke-NUS Signature Research Programme in Cardiovascular and Metabolic Disorders.

Work previously published by Prof Silver demonstrated that Mfsd2a was the primary transporter for the uptake of DHA across the BBB in the chemical form of lysophosphatidylcholine (LPC). This was proven in mouse models and shown to be true in humans as well.

Illuminating angiogenesis

 

Pictured here is a human umbilical vein endothelial cell (HUVEC) created using a super-resolution microscope (ELYRA PS.1, Zeiss). The nuclei can be seen here in blue, cytoskeleton in green, and the mitochondria in red. HUVECs were employed as a model system in a study, published in Nature Communications, that investigated how the gene, Wars 2, controls angiogenesis or blood vessel formation. More about Wars2 and its angiogenetic function can be read here

Image by Mao Wang, Research Assistant in the Cardiovascular and Metabolic Diseases Programme 
Duke-NUS Medical School

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