A Research Blog

Colour my heart red

 Stem cell-derived human muscle fibers in an infarcted mouse heart are shown in this colourful image. Human cells are marked in green and the heart muscle is marked in red. The blue colour that can be seen is the cell nucleus.

Image by Chong Li Yen, a Research Associate in the laboratory of Professor Karl Tryggvason, 
Tanoto Foundation Professor of Diabetes Research
Cardiovascular and Metabolic Disorders Programme
Duke-NUS Medical School

Last time, we looked at Zika and microcephaly. As we continue our series on the top research stories of 2016, we asked Prof Stuart Cook, Director of the Cardiovascular and Metabolic Disorders (CVMD) Programme at Duke-NUS, for what he thought was the biggest research story of 2016 to impact CVMD research. His pick: the Exome Aggregation Consortium (ExAC). In today’s post, we find out more about ExAC and why it is such a big deal.

What ExACtly is the exome?

Our genome stores all the information necessary for life, it is like the body’s instruction manual on how to function. Each cell refers to this manual to determine which genes to express into proteins, thereby dictating a cell’s behaviour within a tissue, organ and system. The portions of the genome that directly code for these proteins make up the exome.

Variation within the exome exists due to the accumulation of mutations in the genome. Some of these variants have no effect on the proteins they code, while others render the protein useless and contributes to the development of disease. The question now is which variants contribute to disease, and which are noise?

What ExACtly is ExAC?

Flora and fauna – in the gut!

Using Periodic acid–Schiff (PAS) staining to indicate the region of basement membrane in human colon tissue, we get to see the unexpected beauty in the tissue.

 Image by Chong Li Yen, a Research Associate in the laboratory of Professor Karl Tryggvason,
Tanoto Foundation Professor of Diabetes Research
Cardiovascular and Metabolic Disorders Programme
Duke-NUS Medical School

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

 

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.

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