A Research Blog

Touted as the most common cause of liver failure worldwide, non-alcoholic steatohepatitis (NASH) manifests as inflammation and increased lipotoxicity in liver cells. Accumulation of fat in the liver has been cited as the cause of NASH. Specifically, the accumulation of saturated fatty acids, such as palmitic acid, in liver cells triggers inflammation, and results in oxidative stress and tissue damage. However, not everyone with fat accumulation in the liver develops NASH. Why is that?

Group photo

Pictured, from left to right: Dr. Jin Zhou, Prof Paul Yen and Asst Prof Rohit Sinha

In their second post, Drs Justin Ng and Chionh Yok Teng from the Bat Pack tell us more setting up the first bat colony for research in Singapore.

First author Dr Mohammad Talaei and co-senior authors Prof Koh Woon-Puay and Prof Yuan Jian Min

A recent study published in the Journal of Nutrition had an interesting finding; Chinese elderly who had consumed milk were less likely than their counterparts to be diagnosed with hypertension. 

Globally, high blood pressure, or hypertension, is the leading risk factor for death associated with cardiovascular disease. A proven, effective way to prevent high blood pressure is adhering to DASH (Dietary Approaches to Stop Hypertension), which includes the consumption of fruits, vegetables, low- or non-fat dairy foods, whole grains, lean meats, fish and poultry, nuts and beans.

The consumption of dairy products is believed to be a key factor in DASH that prevents high blood pressure. This belief has been substantiated by studies in populations that traditionally consume high levels of dairy. What’s interesting about the study, led by NUS’ Saw Swee Hock School of Public Health (SSHSPH) PhD student Dr Mohammad Talaei and his supervisor Professor Koh Woon-Puay from Duke-NUS Medical School and SSHSPH, is that it is the first to show the same positive effect of dairy on high blood pressure, in a Asian population that traditionally has a relatively low consumption of dairy products.

In our final Research Story of 2016, we shift our attention to neuroscience and ask Associate Professor Wang Hongyan, Interim Director of the Neuroscience and Behavioural Disorders Programme at Duke-NUS, for what she thinks is the biggest research story of 2016 to impact neuroscience research. Her pick, a home-grown story literally, is that of the midbrain organoid developed in Singapore by a team from Duke-NUS, A*STAR’s Genome Institute of Singapore and the National Neuroscience Institute.

Making Mini-brains

NBD 2016How does your brain interface so seamlessly with the world? …retain memories? …learn? …determine your personality? And, where does it all go so wrong with neuropsychological disorders? Due to the complexities of the brain and difficulties in accessing human brain tissue for research, these questions have eluded scientists for a long time. Now, researchers are a step closer to answering these questions, by growing brain organoids in the lab. Brain organoids are essentially mini-brains grown in a petri dish, and show remarkable similarity to human brains with the same neural cell populations, 3D architecture and connectivity.

This week, we hear directly from the Health Services and Systems Research (HSSR) Programme at Duke-NUS about their pick for the biggest research story in 2016 to influence health services research. Director of the programme, Professor David Matchar, and Deputy Director, Amina Mahmood Islam, tell us more about non-communicable diseases (NCDs) and how NCDs impact future health services research.

The HSSR Programme considers the increase in chronic, NCDs globally, regionally and in Singapore, the key health services challenge we currently face.

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?

In this week’s Research Story of 2016, we turned to Prof Wang Linfa, Director of the Emerging Infectious Diseases Programme at Duke-NUS, for his pick: the association of Zika infection during pregnancy with microcephaly births. Zika took centre stage in 2016, and will certainly continue to be a main character in research on emerging infectious diseases.

The Zika EmergencyBaby and Mozzie

On 1 February 2016, the world woke up to a new public health emergency: Zika. From then, Zika news hogged the headlines for months, with news agencies charting the spread of infection globally and tracking Zika research.   In the past year, this research has established the association of Zika infection during pregnancy with microcephaly births, while reinforcing the link of Zika infection to increased risk of Guillain-Barre syndrome, a disorder in which the body's immune system attacks part of the peripheral nervous system.

As we say goodbye to 2016 and usher in the new year, the Microscope team would like to celebrate, as we look forward to another year of breakthroughs and advancements, the fantastic year it has been for research. To kick off 2017, we asked each Signature Research Programme Director to pick the top research story impacting their respective research areas in the past year, and have put together a series of posts about each story and its significance for the coming year. Join us over the next few weeks to find out more about the hottest research topics.

In this first instalment, we share with you Professor David Virshup’s pick for the Cancer and Stem Cell Biology Programme at Duke-NUS: Immunotherapy.

What is immunotherapy?Infusions

Immunotherapy has been labelled the newest cancer treatment on the block, a game changer in the way cancer treatment is being approached. Instead of using cytotoxic treatments such as chemotherapy and radiation therapy to kill cancer cells, immunotherapy takes advantage of the patient’s own immune system to recognise and attack cancer cells.

How does immunotherapy work?

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

Many scientists believe the major underlying cause of dementia is the accumulation of clumps of a protein called beta-amyloid, which is a hallmark of Alzheimer’s disease (AD). AD is the most common form of dementia, and it accounts for 60 to 80% percent of dementia cases. Apart from AD, there are many different types of dementia, including some rare types that are inherited or caused by mutations in certain genes. 

Recently, multiple missense mutations in the gene TRIAD3 that result in its loss-of-function have been identified in patients suffering from disorders characterised by cognitive decline, dementia, and movement disorders.  However, it was not clear how TRIAD3 dysfunction resulted in cognitive decline and dementia.

A study by Duke-NUS Assistant Professor Shawn Je, published in Aging Cell, focused on rare mutations in Gordon Holmes syndrome (GHS) patients; these individuals exhibit cognitive decline and dementia. Asst Prof Je’s work was able to show the causal relationship and underlying molecular mechanisms of how the loss-of-function of TRIAD3 resulted in protein misregulation in neurons which, consequently, resulted in synaptic problems and behavioural deficits.

TRIAD3A is an E3 ubiquitin ligase that recognises and facilitates the ubiquitination of its targets for degradation by the ubiquitin-proteosome system (UPS). Asst Prof Je’s laboratory previously identified that this protein regulates a key synaptic protein named Arc (activity-regulated cytoskeletal protein), thereby modulating synaptic transmission in neurons.



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