A Research Blog

Dengue fever, caused by the dengue virus, is a tropical disease transmitted by mosquitoes that threatens more than one third of the worldwide population, making it one of the most important arboviruses in the world. They have important economic consequences because of the burden to hospitals, work absenteeism and risk of death for severe symptomatic cases.

Dengue viruses are primarily transmitted from human-to-human by Aedes aegypti mosquitoes. While the mechanisms leading to dengue infection in humans have been defined, there is a lack of knowledge on how dengue viruses influence mosquito transmission and infection, or the genetic factors that affect virus replication in mosquitoes.

With this quest in mind, researchers at Duke-NUS Medical School’s Emerging Infectious Disease Programme led by Assistant Professor Julien Pompon and Professor Mariano A Garcia-Blanco set out to identify the viral determinants of transmission, as well as the mechanism by which dengue viruses harness evolution to cycle between the two hosts.

Gayatri SharmaWe speak to Dr Gayatri Sharma, Entrepreneur-in Residence (EiR) with CTeD, to find out how an EiR translates Duke-NUS inventions into commercial applications. 

1.       Tell us what you do as an EiR. 

 My primary role as an EiR is to create commercial value for the Intellectual Properties developed at Duke-NUS. Currently, I am working on developing a business plan around a Laminin platform technology developed at Professor Karl Tryggvason’s laboratory. Laminin-based technology enables us to grow cell types sustainably in large numbers by mimicking the environment of a human body. Some of these cell types include keratinocytes (skin cells), islets (insulin-producing cells) and cardiomyocytes (heart cells). This will address the huge market gap in cell production for therapeutic applications. We have seen great results in animal studies, and my job now is to chart the commercial path for this technology. 

 

Mosquitoes

Dengue and chikungunya are mosquito-borne diseases that are currently re-emerging as public health burdens worldwide. Annually, over 390 million people are infected with dengue, while chikungunya periodically emerges in highly populated areas. The primary vector for the two diseases is Aedes aegypti, a mosquito that thrives in domestic areas.

 Since there is no vaccine for these arboviruses, vector control remains the best way to control the incidence of these diseases. In the 1960s, the Singapore government started a vector control campaign in order to prevent the transmission of dengue by Aedes aegypti. Measures included mosquito and clinical surveillance, public health education, community participation, fines for allowing mosquito breeding, among others. While this campaign drastically reduced the number of households with Aedes mosquitoes and the incidence of dengue in Singapore until the 1990s, dengue epidemics have since increased in frequency, and chikungunya re-emerged in 2008.

 To better understand this paradoxical situation Principal Research Scientist Ian Mendenhall and Assistant Professor Julien Pompon from Duke-NUS Medical School (Duke-NUS) led research that investigated whether peridomestic areas, or areas near inhabited areas, could be the cause or source of these diseases.

Esther GanDr Esther Gan, recent Duke-NUS Medical School PhD graduate and speaker for her class shares with Microscope about her journey to Duke-NUS and her plans post-graduation.

How did you first learn about Duke-NUS?

I heard about Duke-NUS from one of my immunology professors during my undergraduate studies at the University of British Columbia.

I have always been interested in infectious diseases research and my experience in an influenza laboratory further piqued my interest in pursuing this avenue. Coincidentally, Dr Ninan Abraham had a collaborator, Dr Veronika von Messling, who had just moved to Duke-NUS to set up a lab and he highly recommended that I did a year of research with her. She was a veterinarian studying the pathogenesis of influenza in animal models. I ended up working for her for a year as a research assistant. It was amazing the amount of techniques that I learnt from her! We worked with mice, ferrets and monkeys all within a span of a year.

We see that you started your Duke-NUS journey as research assistant and not a PhD student. Why didn’t you jump right into the PhD programme and what finally made you decide to take the plunge?

I didn’t know how I would adjust to Singapore culture – the people and the research - after so many years abroad. My idea was to come, work for a year and assess if it would be a suitable place to do my PhD.  It was tough; I missed the nature, the four seasons, the ability to drive two hours and immediately hit a ski slope. But it wasn’t impossible; I did manage to adjust to life here!

That is the question. As the number of end-stage renal disease (ESRD) patients rises rapidly in Asia, the need for dialysis grows with it, along with a trend to start dialysis earlier in the management of ESRD. The situation in Singapore is similarly bleak. It is imperative to determine if the benefits of starting dialysis earlier is worth the high cost and inconvenience that accompanies it, especially when evidence supporting those benefits is limited and controversial.

Team Photo

The research team (L-R): Dr Feng Liang, Professor Tazeen Hasan Jafar, Dr John Carsen Allen.

Daryl Tan

The third year of research is a hallmark of the MD programme at Duke-NUS Medical School (Duke-NUS), which gives students a chance to flex their investigative muscles and figure out ways to treat diseases, improve patient care, better understand patients– or really do any kind of research that will improve people’s lives.

Daryl Tan really made the most of his third year at Duke-NUS. His biggest takeaway from the unique experience was that he learned to seize opportunities to work with the best mentors, to present his research in international conferences and to win prizes for his work.

During his second year elective in Women’s Anaesthesia in KK Women’s and Children’s Hospital (KKH), Daryl encountered brilliant, passionate and pro-teaching anaesthetists. For his third year, it was a natural choice for Daryl to do research at KKH under the mentorship of Associate Professor Sng Ban Leong, Director, KK Research Centre and Deputy Head and Senior Consultant, Department of Women’s Anaesthesia, KKH, and Professor Alex Sia, former Chairman Medical Board and Chief Executive Office and Senior Consultant, Department of Women’s Anaesthesia, KKH.

Cheung Yin BinAs part of an international research collaboration, Professor Cheung Yin Bun of the Centre for Quantitative Medicine (CQM) at Duke-NUS Medical School, developed a set of gestational weight gain (GWG) charts and published them in the prestigious American Journal of Clinical Nutrition [1]. Using prospectively collected weight measurements of pregnant women from 14 to 41 weeks of gestation and statistical methodology for longitudinal data analysis, the team developed not only a conventional, cross-sectional GWG chart but also longitudinal GWG charts, which takes prior weight status into account. That is, the (longitudinal) GWG chart for a woman is calibrated according to her weight in the previous visit, as opposed to using one chart for all women or one chart for a woman at all time.

Assistant Professor Owen Rackham from the Duke-NUS Centre for Computational BiologyAssistant Professor Owen Rackham, from the Centre for Computational Biology at Duke-NUS Medical School, shares more about a study he co-authored on long non-coding RNAs.

In recent years a great deal of attention has been focused on understanding the parts of our genome that don’t encode for proteins. A landmark study has mapped out these poorly understood and highly controversial class of genes, known as long non-coding RNAs and in doing so has found evidence of evolutionary selection and links with major diseases, including cancer.

This is the latest work from the FANTOM5 consortium, an international group of researchers whose aim is to annotate and understand the genome led by RIKEN - Japan's largest research institute for basic and applied research. I am a member of FANTOM5 and coauthor of the findings that were published in Nature last month.

The work involved generating a comprehensive atlas of 27,919 long non-coding RNAs and summarised, for the first time, their expression patterns across the major human cell types and tissues.

By intersecting this atlas with genomic and genetic data, their results suggest that 19,175 of these RNAs might be functional, hinting that there could be as many, or even more, functional non-coding RNAs than the approximately 20,000 protein-coding genes in the human genome.

mosquito

In 2016, the Zika virus dominated all other public health concerns. It was an epidemic in South America and threatened to become one in Asia. Zika is a flavivirus that is mainly spread by the bite of an infected Aedes mosquito. Symptoms range from mild fever to body aches, while an infection during pregnancy could cause foetal brain defects, such as microcephaly.

This year Zika isn’t the hot topic that it was, but it remains a research priority and health concern.

Recently, Assistant Professor Julien Pompon and his team, from the Emerging Infectious Diseases Programme at Duke-NUS Medical School (Duke-NUS), published research that identified the main carrier for an Asian Zika virus strain and compared different Zika virus strains. This work increases our understanding of the virus transmission.

Asst Prof Pompon compared the susceptibility of Aedes aegypti, Aedes albopictus and Culex quinquefasciatus to an Asian Zika virus strain (H/PF13). The mosquitoes from these species were orally fed infected blood and, at seven days post infection, were examined to determine their infection rate and genome copies of the virus. High infection rates and genome copies indicate that the mosquito is more susceptible to picking up and transmitting a virus.

Asst Prof Julian Lim from the Duke-NUS Centre for Cognitive Neuroscience

There are times in a person’s life when sleeping enough doesn’t seem possible. Most of these times tend to coincide with having to take final exams. So, the question is, when a person is sleep deprived, should they take a nap, take a break, or power through and keep studying - for the best result?

This question was answered in a recently published Journal of Sleep Research study by a team of researchers from the Centre
for Cognitive Neuroscience (CCN) at Duke-NUS Medical School (Duke-NUS).

Many things affect cognitive performance. Some of these factors include circadian rhythms, taking a rest break and how long a person spends doing a continuous task. However, how these factors interact to influence cognitive performance is poorly understood.

To shed more light on this topic, Assistant Professor Julian Lim and team from the CCN decided to investigate the effects of napping on the processing speed of a sleep restricted person. Processing speed, or how quickly a person is able to carry out simple or automatic cognitive tasks, is an important contributor to cognitive performance.

The study observed 57 healthy adolescents (26 female, 31 male, aged 15 to 19) as part of the CCN’s Need For Sleep 2 study. In the course of this study, participants were sleep deprived. They were allowed to sleep for five hours a night, over five days, which was followed by nine hours of recovery sleep for two days.

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