Voices from A*STAR

  • Chatting with a Cosmonaut, Part 1

    Tags: aerospace engineeringcosmonautspaceOffice of Research Development and CollaborationThe University of Sydney

    somethingr%2540nature.com

    Lia Paola Zambetti

    Senior Project Officer

    Office of Research Development and Collaboration, The University of Sydney

    When the renowned Russian cosmonaut and space flight veteran Anton Shkaplerov was in Singapore for a series of events, our guest writer Dr Lia Zambetti interviewed him, via a translator, about his experiences in space (and beyond!), and the main challenges faced in space exploration today.

    Lia: Would you please introduce yourself?

    Anton: My name is Anton Shkaplerov, I am a cosmonaut and a jet pilot and I come from the military. I flew in space twice, the last time it was last year [2015]. 

    Lia: How relevant is science for space exploration in 2016 – and beyond?

    Anton: We fly to space to make experiments that are not possible to do on Earth, and the most important thing [to consider] is gravity. It helps being far from the planet, which means we can explore our planet from outside. We can also explore space without having the impediment of atmosphere. 

    In terms of concrete applications, for example, we can produce different types of crystals, which are then used in computer chips. These crystals [need to] have an ideal structure that is impossible to produce on Earth — because of gravity. Space gives us a chance to grow the almost ideal crystalline structure — the better, the more precise and ordered the structure is, the better the performance of the computer will be. 

    Lia: Space work is one of the catchiest forms of scientific exploration/research — what strategies would you recommend to attract interest in sciences that are not so catchy (e.g., any earth-bound research)?

    Anton: The time of colonization of other planets will come soon, because Earth’s population is growing fast and soon our planet won’t be able to feed this [increasing] number of people. That’s why we need to explore other planets. That’s the future. So, in order to do this, we need to improve the science and develop new techniques to make this happen. So if the scientists want to help this situation they need to improve their knowledge in space programs. 

    Lia: What have you learnt from your fellow scientist colleagues (both on and off Earth)?

    Anton: To make experiments in space, we need to have [scientific] training here on Earth. For example if we need to explore volcanoes on Earth, we work with scientists who are experts in the field and they explain to us how a volcano works, how it explodes, how it all functions and everything else that is necessary [for the mission]. And before every experiment we have a consultation and session with the scientists [involved] on what the experiment will be about. So, besides being a pilot, I was forced to learn a lot more things as a cosmonaut. But it was fun!

    Lia: Where do you think mankind will be able to reach in, say, 20 years from now and how do you see the far future (say, 100 years from now)?

    Anton: In 20 years, we will use the International Space Station (ISS) again. I hope that new spacecrafts will be launched, from Russia, America and other countries as well — and I also hope there will be also commercial partners, such as Elon Musk [and his company SpaceX]. In 100 years, we will be able to reach Mars and even further. 

    Stay tuned for the second part of our interview with Anton, where we discuss his thoughts about Singaporean space travel and space food!

    About the interviewee

    Anton Nikolaevich Shkaplerov was born on February 20, 1972, in Sevastopol, Crimean peninsula. He graduated from the Kachinsk Air Force Pilot School in 1994 as a pilot-engineer. After graduating from the N. E. Zukovskiy Air Force Engineering in 1997, he served as a senior pilot-instructor in the Russian Air Force. He flew 3 different types of aircraft: Yak-52, L-29 and MiG-29. In addition to being a Class 2 Air Force pilot-instructor, he is also an Instructor of General Parachute Training.

    Shkaplerov was selected as a test-cosmonaut candidate of the Gagarin Cosmonaut Training Center Cosmonaut Office in May 2003. From June 2003 to June 2005 he attended basic space training and in 2005 he qualified as a test cosmonaut. He served as a Flight Engineer for Expedition 29/30 (2011-2012) and in Expedition 42 (2014-2015), flying to the ISS with Barry Wilmore and Terry Virts from the USA, Alexander Samokutyaev and Elena Serova from Russia, and Samantha Cristoforetti from Italy.   (Adapted from here)

    Dr Lia Paola Zambetti is a scientific journalist and avid science communicator, with over seven years of experience as a researcher in Immunology. She is currently a Senior Project Officer at the University of Sydney’s Office of Research Development and Collaboration, where she manages a fellowship programme and offers strategic advice, training, and mentoring to scientists.

  • Unraveling the Hidden Truth: Text and Context

    Tags: geneticsepigeneticsmemorytransgenerational inheritanceasthmaair pollutionSingapore Immunology Network

    Anand Andiappan

    Senior Research Scientist

    Singapore Immunology Network

    The Singapore Immunology Network (SIgN) aims to advance human immunology research and participate in international efforts to combat major health problems. Researchers at SIgN investigate immunity during infections and inflammatory conditions, including cancer, using both mouse models and human tissues.

    In the last post, we were discussing that there is more to traditional genetics that affect our risk for disease. We all know that the genetic code of DNA is made up of the bases A (adenine), T(thymine), G(guanine) and C(cytosine). Just like any language, meaning comes from reading letters in context. To understand DNA, the language of genetics, we need the context of epigenetics. The basis of health and disease could be understood if we understand how to read the text in context.

    The secret in genetics – epigenetics!

    The term epigenetics refers to heritable traits 'outside of' genetics. So what causes these changes in addition to the effects of the genetic sequence? It can be anything from air pollutants, allergens, microbes, diet and toxins, among others. Genetics refer to the part of your DNA which doesn't change over the years. However the epigenetics of your DNA can and do change! While genetics are the physical code consisting of nucleotides, there are chemical switches, or 'epigenetic tags', which can turn genes on or off without altering the genetic code. This is a fascinating new area of research which helps us understand how our genes and the environment we are exposed to lead to diseases.

    Do our genes have memory?

    For a long time, we did know that we inherited our genes from our parents. With epigenetics however, we are now seeing evidence that we might also inherit the environment or experience of our parents. In one study of this surprising phenomenon, male mice were trained to fear a specific odor by receiving an electric shock upon exposure. When these mice had babies, they too were afraid of the odor, as were their offspring, the 'grandchildren' of the trained mice. These two generations of rats had not been trained by shock on odor exposure. However the scientists observed that both the father and the babies had epigenetic tags that associated with additional neurons in the nose and altered activity in the brain. Mice! What about humans?

    Context matters!

    At the population level, there seems to be some evidence for transgenerational inheritance.Data from the Netherlands, where the population suffered a famine in the winter of 1944-45, showed that children born during the famine were smaller and had higher risks of obesity, cardiovascular diseases and mental disorders as adults. Strikingly, they in turn had children who were smaller, even though they had improved living conditions. Although this is still observational, it makes us wonder if our exposure and experience could affect both our offspring and their children. In particular, what about asthma and allergies?

    It's all in the family!

    Smoking and air pollution are strong environmental risk factors for asthma. Recent evidence shows that exposure to air pollution during pregnancy is associated with changes in the epigenetic pattern of the newborn in stress-related genes. Interestingly, the smoking status of a grandmother during her pregnancy is associated with her grandchild's risk for asthma, even if the grandchild's mother didn't smoke. In a study of the parents of 24,168 offspring, fathers who smoked during adolescence increased the risk of their children having asthma by 3-fold. So there is some evidence that risk for disease involves more than just the genetic code in DNA. The main issue, however, is that most studies have been looking at either genetics or epigenetics, few studies look at both.

    We can't simplify what's complex!

    At this point in time, we have only started scratching the surface of this vast field of epigenetics. It's exciting to see that there have already been some exciting findings which hold great promise! However, we need to be careful not to ignore the complexity of complex diseases such as asthma, diabetes, obesity, cardiovascular diseases, and so on. We need to carefully document the genetics and epigenetics in the context of environmental exposure, family history and possibly even population history. Our group along with our collaborators have started doing this to study allergies and asthma.

    Dr Anand Andiappan is a Senior Research Scientist at the Singapore Immunology Network. For over a decade he has been studying allergies, particularly focusing on allergy prevalence in Singapore. He graduated with a doctorate in biology from NUS and has been since working with A*STAR. He also collaborates with allergy researchers worldwide to understand the unique situation in Singapore better. His current research focus is to understand the risk factors related to manifestation of allergies by studying the underlying genetics, epigenetics and corresponding immune responses in individuals. 

  • Allergies are Not to be Sneezed at!

    Tags: coldallergicasthmasneezehay feverallergen-specific immunotherapySingapore Immunology Network

    Anand Andiappan

    Senior Research Scientist

    Singapore Immunology Network

    The Singapore Immunology Network (SIgN) aims to advance human immunology research and participate in international efforts to combat major health problems. Researchers at SIgN investigate immunity during infections and inflammatory conditions, including cancer, using both mouse models and human tissues.

    Have you ever suffered from asthma or know someone who does? It is excruciating to watch them suffer. An asthma attack makes something as simple as breathing, extremely difficult. I have seen this first hand with my mum, brother and sister, who are all asthmatic. Asthma is just one of the allergic diseases that grip our lives — rhinitis and eczema, that affect the nasal passages and skin, respectively, are also very common in Singapore. “How common?” you may ask? 

    Let’s talk numbers!

    In a study published in 2014 my colleagues and I found that almost half of the nearly 8,000 people surveyed had one of these three conditions. Allergic rhinitis (AR), known more commonly as ‘hay fever’ in the western world, affects nearly 40 per cent of the survey respondents, while asthma affects nearly 20 per cent. 15 per cent of volunteers said they had eczema or atopic dermatitis, often caused by allergens.There is also a worrying trend that the prevalence of allergies is increasing worldwide, and Singapore is not spared from this. Children’s hospitals in Singapore report asthma prevalence in kids to be around 25 per cent and AR over 40 per cent. So what causes the allergies that lead to these conditions?

    The culprit!

    We tested the blood of nearly 600 people for antibodies against common allergens. Antibodies are proteins specific to foreign substances that enter our body. The antibody ‘IgE’ is unique to allergens. About 80 per cent of these individuals had antibodies against house dust mites. We verified this finding in a study of over 7,000 volunteers where we found the rates to be similarly high, nearly 75 per cent. This was a startling find; especially given we didn’t find many antibodies for other common allergens such as pollen, molds and pet dander (hair and dead skin cells). People who had a history of asthma and AR had about ten times more IgE antibodies in their blood compared to those who didn’t. So we hypothesize that the prevalence of asthma and AR could be associated with the house dust mite allergy. But we still lack exact mechanisms to explain how this dust allergy leads to specific clinical manifestations. Interestingly, we had an exciting finding when we continued looking at the immune system. What did we find?

    It’s not all bad… there is help!

    When we looked at one particular subset of immune cells called ‘basophils’ in the blood of nearly 500 of the participants of the study, we found something peculiar. Basophils are supposed to sense allergens and release molecules which lead to allergy symptoms. In nearly 10 per cent of these individuals, most basophils didn’t seem to sense the allergen tested which was house dust mites in this case. Their IgE antibody levels were also reduced. This reduced response called ‘basophil anergy’ was naturally occurring in some individuals, who also had reduced or no nasal allergies. So basophil anergy appears to reduce the risk for AR. Why is this important?

    Can we be at ease without sneeze?

    We are very excited with the above finding because, we can use this naturally occurring phenomenon to understand how we could potentially treat patients with nasal allergies. One of the treatments for AR is ‘allergen-specific immunotherapy’. Here the patient is given small doses of the allergen over a longer period of time to help train the immune system to tolerate the allergen. Could it be that our phenomenon of basophil anergy is one of the mechanisms that controls this training? We don’t know yet, but we can find out! For this, we need to work with the clinicians who actually see the allergy patients day in and day out. We are currently working together with local clinicians and pharmaceutical companies to try to understand the cause of allergies, develop drugs and help better treat patients.

    Treatment: One size doesn’t fit all

    Currently there is no cure for allergies, although effective treatments are available. Asthma control, however, is still a concern. While most patients respond to treatment, about 510 per cent of asthmatics unfortunately don’t and have frequent attacks and are hospitalized as a consequence. Some studies have shown that this could be due to mutations in genes which could cause the treatment to fail. We have now initiated a global partnership to understand why it’s difficult to control asthma in some asthmatic children. This effort is called Pharmacogenomics in Childhood Asthma (PiCA). With genetic data from nearly 15,000 children from 12 countries with asthma status and medication usage, we aim to develop personalized treatments for every asthmatic.

    So, what next?

    We know that allergies are inherited. Children with parents who have had allergies are at a higher risk to develop allergies themselves. However, we don’t exactly know what the causes are for the manifestation of allergic diseases like asthma and allergic rhinitis. Is it mutations (genetic changes) we inherit from our parents? Or the environment we live in?

    The answer could lie somewhere in between, in a new and exciting field of research called “epigenetics”, which I will explain at length in the second installment of this two-part series.

    Dr Anand Andiappan is a Senior Research Scientist at the Singapore Immunology Network. For over a decade he has been studying allergies, particularly focusing on allergy prevalence in Singapore. He graduated with a doctorate in biology from NUS and has been since working with A*STAR. He also collaborates with allergy researchers worldwide to understand the unique situation in Singapore better. His current research focus is to understand the risk factors related to manifestation of allergies by studying the underlying genetics, epigenetics and corresponding immune responses in individuals. He will also be giving a talk on this topic at the upcoming one-north Festival on August 19. Click here to find out more.

  • An Adult’s Perspective on Children’s Portion Size

    Tags: NutritionObesityPortion sizeSingapore Institute for Clinical Sciences (SICS)

    Keri McCrickerd

    Research Fellow

    Singapore Institute for Clinical Sciences

    Established in 2007, the Singapore Institute for Clinical Sciences (SICS) conducts needs driven, impact-focused research to promote the health and human capacity of Singapore. SICS is distinguished by its focus on clinical sciences and the use of innovative approaches and technologies that enable the efficient and effective study of human health and diseases. The clinical scientists in SICS conduct the full spectrum of "bench to bedside" research activities.

     

    © 2017 A*STAR Singapore Institute for Clinical Sciences

    Adults influence children’s eating behaviors

    Children develop their eating behaviors in the environments they grow up in, and whether at home, in childcare or out in eateries, adults determine the quality and quantity of children’s food provisions. 

    Serving size matters 

    Childhood obesity is a serious public health concern in Singapore and around the world, partly caused by the frequent consumption of large portions of calorie rich foods.  

    Adults and children tend to eat more when served large portions. Research investigating ‘The Portion Size Effect’ has shown that children as young as 2 years old eat more when served larger-than-normal portions at meal times. This effect is strongest in foods we like the most, which unfortunately are not typically the wholegrains and vegetables we actually want children to eat more of.

    The unique role of childcare in Singapore

    The Early Childhood Development Agency reports that 99 per cent of pre-school age children (6 years old and below) attend a pre-school center, where they often eat several meals and snacks. This places childcare providers at the heart of a child’s early food environment.

    In a study recently published in the Journal Appetite, we investigated the influence of portion size on children’s lunch intake in a local pre-school. We found that the portions children were served by their teachers were very similar to those the children would serve themselves. This means that, in this particular school, the teachers were relatively ‘in tune’ with the children’s individual portion needs and average portions served to children were in-line with those recommended by Singapore’s Ministry of Health (MOH) and Health Promotion Board (HPB).

    Importantly, when the teachers were asked to serve a bit extra at lunch (about 50 per cent more than each child’s usual lunch intake), the children ate more. This Portion Size Effect was strongest in the oldest children (5–6 years old), who ate everything they were served, and weakest in the young children (2–3 years old), who consistently had leftovers in their bowl.  This shows how the portions adults pick can influence how much children eat, especially if children are encouraged to eat everything served. 

    Portion Distortion

    So how do adults know how much to serve growing pre-school age children? 

    In Singapore, pre-school centers like the one we studied can follow the HPB’s Healthy Meals in Child Care Centres Programme for guidance on menu-planning, healthier cooking methods and age-appropriate portion sizes.  

    A potential problem is that younger children (less than 4 years old) rarely consume fixed portions and often eat different amounts depending on the meal or day. In reality, appropriate portions depend on a range of factors, including the size of the child’s previous meal, their height, weight and activity level. This variability can lead parents and caregivers to question whether standardized portion guidelines actually apply to their child.  

    Some parents report ‘just knowing’ the portions to serve their child. But adults could unintentionally serve too much if portion decisions are biased by factors unrelated to the child’s needs, such as serving children portions you would like to eat, or not believing children are full when they are say they are.

    Adults have a role to play in healthy portion decisions

    It is important to recognize that portion sizes will only be problematic if they are consistently inappropriate for a child’s age, size and activity level. 

    If a young child is showing healthy weight gain as they grow (e.g. is not underweight or overweight for their age and height), the portion sizes they are consuming day-to-day are probably appropriate for their needs.  Here, urging children to finish everything on their plate may be unnecessary and could prevent children attending to their own feelings of hunger and fullness. 

    There is a need for public health professionals to better understanding of how parents and caregivers make portion decisions for children, and assess the use of existing portion guidelines. With such a high rate of preschool childcare attendance, Singapore is in a unique position to be at the forefront of promoting appropriate portion sizes so all adults can support healthy growth in children.   

    Dr. Keri McCrickerd is an Experimental Psychologist based in the Clinical Nutrition Research Centre (Singapore Institute for Clinical Sciences). As part of the Sensory and Ingestive Behaviour research team, she investigates the development of eating behaviours and appetite control mechanisms in children and adults, in both laboratory and school-based studies as well as within the GUSTO cohort. 

  • Jenner’s Legacy, Part 2: Challenges in Creating Ideal Vaccines for Modern Infectious Diseases

    Tags: ImmunologyVaccinationSingapore Immunology Network (SIgN)

    Kaval Kaur

    Research Fellow

    Singapore Immunology Network

    The Singapore Immunology Network (SIgN) aims to advance human immunology research and participate in international efforts to combat major health problems. Researchers at SIgN investigate immunity during infections and inflammatory conditions, including cancer, using both mouse models and human tissues.

    Welcome to Part 2 of Jenner’s Legacy.  Following on from my discussion of Jenner’s pioneering work in smallpox vaccination, here I will explain why it’s so difficult use this approach to develop ideal vaccines for influenza and dengue.

    Inoculating against Influenza

    Influenza is a viral disease that we are all too familiar with.  Although we often think of the influenza virus as a single pathogen, the virus is in fact extremely varied.  There are two main types of influenza viruses that infect humans, influenza A and B, and these are further characterized into different subtypes and lineages.  Within each subtype, there are also numerous strains.  A wide variety of influenza strains exist because the influenza virus is continuously evolving through an ongoing process of mutations, which alters its surface proteins.  New influenza strains also emerge when two or more viruses present in a single host recombine their viral segments to generate a dramatically different strain, such as the most recent 2009 pandemic H1N1 strain.

    The ability of the influenza virus to constantly mutate and change allows it to fool the body’s natural immune response.  Our body’s immune system combats the influenza virus by producing antibodies that bind to the virus’s surface proteins.  If these surface proteins were constant from one strain of influenza to the next, Jenner’s methodology for vaccines would work brilliantly with the power of immunological memory, saving millions from the horrors of flu season every year.  Unfortunately, it is precisely the variable surface proteins to which majority of the antibodies of the immune system bind.

    However, that does not mean that antibodies produced from an influenza vaccination are entirely without use.  Antibodies produced in response to a particular strain of influenza are effective in protecting the body from future infections of that particular strain and similar strains.  In fact, this effect is the primary driving force behind the modern influenza vaccine that millions take each influenza season.  Every one to three years, the influenza vaccine is reformulated to contain the strains that are predicted to circulate in the upcoming influenza season.  When the vaccine strains match the circulating strains, there is good protection against influenza infections.  However, the predictions of which strains will circulate in a particular influenza season are not always accurate, and they cannot account for the unexpected emergence of recombined strains.  When mismatches between vaccine strains and those that infect in a given season occur, the vaccine does not provide the desired level of protection.  Hence, while the current influenza vaccine has tremendously reduced influenza infections and deaths, it is not yet an ideal vaccine that can provide complete coverage against all influenza strains.

    Mounting a defense against dengue

    Similarly, the dengue virus is another infectious agent characterized by many different virus types.  There are four distinct serotypes of dengue viruses (DENV1 to DENV4) that share 60–80 per cent similarity to each other.  To provide coverage against all 4 serotypes of the virus, the simplest strategy for a vaccine is to include all four serotypes in the vaccine formulation.  Indeed, Dengvaxia, the first dengue vaccine to be approved for human use in Mexico, Philippines and Brazil, employs this approach.  While Dengvaxia provides strong protection against severe dengue, it is far from a perfect vaccine.  Efficacy against each serotype is varied, with the lowest efficacy seen for DENV2, at only 42 per cent.  Furthermore, due to lower efficacy in the young and old, the vaccine is only approved for persons between the ages of 9 and 45, leaving vulnerable age groups without any protection.  Scientists are still trying to determine why such an approach to dengue is not entirely effective and why Dengvaxia fails to be the one-stop solution for dengue.

    Even though the diversity of the dengue virus poses some challenges for dengue vaccine development, it is really the nature of our natural immune responses against dengue that have scientists truly stumped. Upon first infection with any one of the four serotypes of dengue, our immune system gets activated and produces antibodies that bind not only to the infecting serotype but also the other three.  Referred to as cross-reactive antibodies, these kinds of antibodies against viruses are generally beneficial as they can provide a wide breadth of protection against future infections with different strains.  However, this is not the case with the dengue virus.  For reasons still unclear to scientists, cross-protection for the other serotypes is only short-term and life-long immunity is achieved only against the infecting serotype, but not the other three serotypes. Further, previous infection with dengue actually puts a person at risk of having more severe dengue upon secondary infections with different serotypes! This is a significant problem in regions where dengue is endemic and individuals are often infected more than once.  Scientists believe that although normally, antibodies with viruses bound are taken up by innate immune cells for the viruses to be destroyed within the cell, during a secondary dengue infection, cross-reactive antibodies weakly bound to dengue virus actually serve to facilitate viral entry into the immune cells, where the virus replicates and increases the level of infection.  Manipulating our immune responses to prevent such a phenomenon will be crucial in reducing the severity of secondary infections with and is currently a vibrant area of investigation.

    Moving beyond Jenner 

    While Jenner’s insights were brilliant and have revolutionized modern immunology, his straightforward approach to vaccination does not work for all infectious agents and we have many infectious diseases today that remain ‘unsolved’. Research on developing effective vaccines must now focus on rational vaccine design tailored to the complexities and nuances of a given infectious agent.  Vaccine formulations can no longer be restricted to contain solely dead or weakened whole viruses or bacteria.  Instead, scientists must make informed decisions by identifying the components of disease-causing agents that are most relevant for our immune system to recognize and develop long-lasting memory.  For instance, to get ahead of the ever-changing influenza virus, scientists are trying to reinvent the influenza vaccine by directing their research efforts on those vital viral proteins that do not mutate from strain to strain, but instead remain constant in all influenza types. In the case of dengue, while several other vaccine formulations are being tested in clinical trials, research efforts are focused on bridging our knowledge gaps on the interaction between our immune system and the dengue viruses.

    My research is focused on furthering our understanding of the characteristics of human antibody responses during primary and secondary dengue infections.  There is still so much we don’t understand about human immune cell responses after a dengue infection.  As we learn more about how our immune system responds to the dengue virus and what is needed to acquire long-term protection, we can uncover strategies that can be leveraged during vaccine design.  And so, scientists like myself will continue to work at finding the answers to the problems posed by disease-causing agents like the influenza and dengue viruses. Hopefully, our answers will come sooner rather than later and we can rid the world of two more infectious diseases.  

    Dr. Kaval Kaur is a research fellow in Katja Fink’s laboratory at the Singapore Immunology Network. She was awarded the NSS-PhD scholarship to study immunology at the University of Chicago. She enjoys many different topics within immunology, but it is the interplay between viruses and the immune system that has always captivated her. Her research interests include the role of B cells and antibodies in the fight against the many viruses that invade us and investigating how we can manipulate the responses of the immune system for vaccine development. For her graduate studies, she focused on influenza and now, at SIgN, she has turned her attention to dengue.

  • Jenner’s Legacy, Part 1: How Smallpox Was Eradicated with Vaccination

    Tags: ImmunologyVaccinationSingapore Immunology Network (SIgN)

    Kaval Kaur

    Research Fellow

    Singapore Immunology Network

    The Singapore Immunology Network (SIgN) aims to advance human immunology research and participate in international efforts to combat major health problems. Researchers at SIgN investigate immunity during infections and inflammatory conditions, including cancer, using both mouse models and human tissues.

    Over 200 years ago, smallpox was devastating humankind — 20 to 60 per cent of infections were fatal and those who survived were plagued with disfiguring scars and often went blind.  The deadly disease was feared by everyone except milkmaids, who intriguingly were immune.  An English physician and scientist, Edward Jenner, observed that milkmaids had blisters caused by cowpox, a disease similar to smallpox but much less dangerous, and hypothesized that having cowpox protected these milkmaids from smallpox.  In 1796, he went on to test this experimentally.  He took pus from the fresh cowpox blisters of a milkmaid and inoculated an 8-year-old boy — while it may be disconcerting from a modern viewpoint, inoculation was a standard medical practice at that time. Weeks later, Jenner inoculated the boy again, this time with pus from fresh smallpox blisters.  The boy did not contract smallpox and it was concluded that he was protected from the deadly disease.

    This simple, yet incredibly significant, piece of evidence went on to lay the foundations of vaccination and revolutionize modern immunology.  Scientists quickly realized that Jenner’s strategy of vaccination — inoculating a person with a less dangerous version of the disease-causing agent to provide future protection against the disease — was a powerful tool to tackle a host (no pun intended) of infectious diseases.  Over the years, the crowning glories of immunology have been the successes of vaccines as diseases such as smallpox, Rinderpest, and wild polio type 2 have been eradicated, while many others such as measles, mumps, rubella, tetanus and diphtheria have been significantly controlled and are on the road to elimination.

    While Jenner’s strategy of vaccination has been successfully validated time and time again over the past two centuries, it is only in recent years that scientists have determined how vaccination actually works.  When vaccines containing dead or weakened disease-causing agents — such as viruses or bacteria — are injected into the body, they prime the immune system to react, but do not actually trigger the disease.  Cells of the immune system recognize the vaccine components as foreign and launch an immune response, reacting as if it was a real attack.  Antibodies are produced, and activated immune cells go on to populate the long-term memory compartments of the immune system.  If the body encounters the same disease-causing agent in the future, pre-existing antibodies will neutralize it while memory cells will react rapidly to clear the invader before it can gain a foothold and cause disease.  The ability of vaccines to harness the power of immunological memory and provide future protection against disease gave the scientific community confidence that we had capacity to fight against all infectious diseases.

    Unfortunately, as scientists began applying Jenner’s methodology of smallpox vaccination to other infectious diseases, it became clear that his strategy was not a ‘one-size-fits-all’ approach.  Numerous diseases present challenges that make developing highly effective vaccines, with the dead or weakened versions of the disease-causing agent, very difficult.  Influenza and dengue, are excellent examples of such diseases — both are caused by complex viruses and the body’s natural immune response to them makes Jenner’s straightforward approach to vaccination fall short. 

    Stay tuned for Part 2 of Jenner’s Legacy, in which I will discuss the challenges in developing vaccines for Influenza and dengue.

    Dr. Kaval Kaur is a research fellow in Katja Fink’s laboratory at the Singapore Immunology Network. She was awarded the NSS-PhD scholarship to study immunology at the University of Chicago. She enjoys many different topics within immunology, but it is the interplay between viruses and the immune system that has always captivated her. Her research interests include the role of B cells and antibodies in the fight against the many viruses that invade us and investigating how we can manipulate the responses of the immune system for vaccine development. For her graduate studies, she focused on influenza and now, at SIgN, she has turned her attention to dengue.

  • Can an orange a day keep the doctor away?

    Tags: Vitamin CObesitySingapore Bioimaging Consortium (SBIC)

    Sandhya Sriram

    Programme Management Officer

    Singapore Bioimaging Consortium

    The Singapore Bioimaging Consortium (SBIC) aims to build a coordinated national programme for imaging research, bringing together substantial strengths in the physical sciences and engineering and those in the biomedical sciences. It seeks to identify and consolidate the various bioimaging capabilities across local research institutes, universities and hospitals, in order to speed the development of biomedical research discoveries.

    © Jonathan Paciullo/Moment/Getty

    Everyone has heard about how an apple a day can keep the doctor away. Well, I have a different take on it — use an orange instead!

    Having worked with antioxidants and oxidative stress (harmful free radicals) for about a decade now, I am convinced that antioxidants are the way to go to prevent or relieve the symptoms of certain diseases — they also help to keep you energetic by detoxifying your body.

    Vitamin C, an antioxidant, is abundant in citrus fruits like oranges, lemons, and limes as well as papayas, guavas, pineapples, and my personal favorite, berries. Vitamin C supplementation has been shown to lower the risk of stroke, relieve common colds, protect against immune system deficiencies, prevent cardiovascular diseases, maintain healthy and wrinkle-free skin and improve eye health. My research, in particular, focuses on the effect of Vitamin C on obesity.

    Excess fat or ‘adipose tissue’ is what leads to obesity and adipose tissue like every other organ consists of stem cells. A stem cell is an undifferentiated cell which is capable of giving rise to more cells of the same type, or of certain different types of cells upon appropriate triggers. My work entails identifying inherent differences during obesity in adipose stem cells from different depots of fat — mainly, subcutaneous fat (‘good’ fat that helps you burn calories, located below the skin) and visceral fat (‘bad’ fat that stores calories, located around the abdominal organs).

    Obesity is a pandemic affecting majority of the world’s population. According to the World Health Organization (WHO), the world is getting fatter — approximately 850 million people were either overweight or obese in 1980, this skyrocketed to 2,100 million people in 2014!

    Obesity is defined by the Body Mass Index (BMI). According to the WHO; a score between 25 and 30 is considered overweight and anything above 30 is obese. Obesity is a metabolic syndrome that is related to arthritis, cancer, infertility, diabetes, heart diseases, stroke and back pain. The best way to avoid becoming obese and reduce your body weight is to follow the ABC rules — Adopt new healthy habits (bike to work, have a balanced diet, swim etc.), Balance your calorie intake and Control your weight gain. Overall, obesity is definitely a preventable disease.

    Being of Indian origin and having lived in Singapore for about 8 years now, I have always thought that the amount of rice consumed by Asians could be harmful. This feeling has been proven right by the latest report that, in Singapore, 4 in 10 adults are overweight and more than 400,000 are diabetic. These are alarming numbers for a nation that has a population of less than 6 million.

    That is why our lab specializes in identifying key characteristics of adipose stem cells that can contribute to obesity and ways to reduce fat accumulation. My research, in particular, is on the effect of Vitamin C on human subcutaneous and visceral adipose stem cells obtained from obese subjects and the mechanism by which it curbs the excess oxidative stress. For now, I can reveal only so much, but stay tuned for more exciting insights from my research in the near future.

    I can, however, tell you this — have an orange a day and keep the fat away!

    Sandhya is a scientist, entrepreneur, serendipitous journalist and a manager. She lives in Singapore currently and wears many hats – Programme Manager at SBIC, A*STAR; Founder & Director SciGlo; Co-founder & Author, Biotechin.Asia, Biotech Media Pte. Ltd.; and a mother of a very active and inquisitive toddler! Until October 2016, she was a Research Fellow at SBIC and also the Vice President & Publicity Chair of the A*STAR Postdoc Society (A*PECSS).

  • Chemotherapy and Infection: The Transformation from Dr Jekyll to Mr Hyde?

    Tags: MutationsSingapore Immunology Network (SIgN)

    Flora Teoh

    PhD Student

    Singapore Immunology Network

    The Singapore Immunology Network (SIgN) aims to advance human immunology research and participate in international efforts to combat major health problems. Researchers at SIgN investigate immunity during infections and inflammatory conditions, including cancer, using both mouse models and human tissues.

    Most people's ideas of bacteria and fungi tend to be negative, since we often think of them only as the cause of many human diseases. Yet we must not forget that the average human body is colonized by trillions of microbes belonging to these microbial groups. In fact, it has been estimated that the number of bacterial and fungal cells colonizing a human far exceeds that of the number of cells actually belonging to the human!

    In a healthy person, these microbes do not cause disease — many of them perform important functions, for example during the production of enzymes that break down food, the development of the immune system and even preventing disease from other microbes. This seemingly neutral relationship with the human host can take a nasty turn if the person's immune system stops working properly, which is often the case for cancer patients who are undergoing chemotherapy treatment. Cancer cells proliferate uncontrollably and rapidly, which is a double-edged sword, as uninhibited cell division enables their growth and invasion but makes them highly vulnerable to chemotherapy drugs that work by interfering with cell division and growth processes.

    However there are many healthy, non-cancerous cells such as those of the epithelial surfaces — which line our gastrointestinal and respiratory tract, among other things — and immune system which also need to undergo rapid cell division in order to maintain their function. As chemotherapy drugs do not distinguish between healthy and cancerous cells, these healthy cells become collateral damage in the war between cancer cells and chemotherapy drugs.

    Ironically, a patient could die from side effects resulting from the cancer treatment rather than from the cancer itself. This is because the immune system and epithelial surfaces are important defenses against microbial invasion and infection, and weakening them via chemotherapy treatment makes it more likely for cancer patients to develop infections, even from microbes that normally peaceably reside in the human body.

    Little is known about whether chemotherapy drugs have any effect on microbes themselves, and whether these effects contribute to the development of disease. Why should this be of interest? Because the targets of chemotherapy drugs present in humans, are often also present in microbes.

    As the processes governing cell division and growth are so crucial to life itself, variations within these processes are not well-tolerated or optimal for life, making them highly conserved in an evolutionary sense: simply put, there are very strong commonalities in these processes from the simplest microbe to the most complex mammal.

    Thus, a chemotherapy drug that affects a component in a human cell can also do so in a fungal cell. Moreover, the manner in which chemotherapy drugs act on cells also tend to produce mutations. What then, might these mutations do? Might the microbial population harbored by a cancer patient treated with chemotherapy drugs be more likely to mutate due to exposure to the drug? Might these mutations make them more likely to cause disease or be more resistant to antibiotic treatment: in short, to transform from Dr Jekyll to Mr Hyde? This is one of the main research questions I am studying in Candida albicans, a fungus which is a major resident of the human skin and gastrointestinal tract, yet is also a common cause of dangerous blood infections in cancer patients.

    A note before we end: this post is not meant to demonize chemotherapy drugs, or discourage people from seeking cancer treatment. That chemotherapy is a painful and arduous course to endure cannot be disputed, but we must also acknowledge that it was for many years, the only form of treatment physicians could offer to cancer patients, and before its advent, a cancer diagnosis was effectively a death sentence. Chemotherapy has prolonged the life expectancy of cancer patients, and together with modern medical interventions, can even produce cancer remission. We therefore should endeavor to avoid throwing the baby out with the bathwater. By learning more about how chemotherapy interacts with microbes and the consequences of such interactions, we may eventually be able to prevent such opportunistic infections in cancer patients, anticipate drug resistance and assist physicians in selection of therapy, ultimately improving the outcome of cancer treatments and the life expectancy of cancer patients.

    Flora Teoh received the A*STAR Graduate Scholarship in 2013 and began her PhD in the lab of Dr. Norman Pavelka, which focuses on studying the ecological and evolutionary forces that shape the interactions between Candida albicans, GI bacteria and the immune system. Her PhD project involves studying how chemotherapy influences the disease-causing ability of C. albicans by changing its behavior and genetic makeup. She applies a combination of molecular biology and immunological techniques, genetic manipulation and experimental evolution in her studies. Teoh’s research interests lie in evolutionary processes, genomics and yeast biology.

  • The impact of the media on scientific research

    Tags: Science communicationBiotechnology

    Sandhya Sriram

    Research Fellow

    Singapore Bioimaging Consortium

    The Singapore Bioimaging Consortium (SBIC) aims to build a coordinated national programme for imaging research, bringing together substantial strengths in the physical sciences and engineering and those in the biomedical sciences. It seeks to identify and consolidate the various bioimaging capabilities across local research institutes, universities and hospitals, in order to speed the development of biomedical research discoveries.

    © miakievy/DigitalVision Vectors/Getty

    “Did you know that cancer can be cured by eating XYZ (type of food) three times a day for just three months?” asked one of my aunts. I was taken aback and immediately told her that it was nonsense and asked her where she heard or read this so-called ‘information’. It turned out that one of her friends had posted it on her Facebook wall and she had assumed it was true without bothering to check the source of the information.

    Limited awareness and ignorance of biotechnology, biological sciences and its role in society has made it difficult for the general public, such as my aunt, to critically evaluate the veracity of clickbait-style health articles.

    The problem with science stories prepared by the mainstream media is that their focus is on increasing their viewership and subscribers, so they have an incentive to report anything and everything — spoon feeding the audience, with questionable fact-checking. This is exacerbated by the fact that many scientists don’t want to or don’t have the time to talk to journalists or corporate communications about their research and discoveries, or don’t bother to write or speak about it in layman’s terms.

    To bridge the gap in public perception and education of biotechnology and other related sciences scientists, doctors and researchers have a responsibility to engage in science communication, which means discussing their work in an intelligible and audience-friendly way. Science communication generally refers to the communication of science-related topics to non-experts and while it often involves practicing scientists participating in ‘outreach’ activities, it has also evolved into a professional field in its own right.

    My partners, Dr Laxmi Iyer and Prasanna Kumar Juvvuna, and I co-founded Biotechin.Asia, a news website for biotech and healthcare news to communicate fact-based scientific research written by scientists, doctors, medical professionals and researchers. Recently, in September 2016, I launched SciGlo, a one-stop solution for scientists which curates fact-based, reliable, science-related articles from all over the world. Both of these sites sought to provide a platform that represented science and scientists correctly and responsibly interpreted and communicated scientific findings to make it easier for laypeople to have access to credible science news.

    Some research institutes, universities and scientists themselves are revisiting scientific communication. Scientists seem to be more willing to speak to the media about their research. The impact of open access and social media on scientific research is catching on, and scientists are using social media to voice their opinions and let the public know if certain news items are bogus. Overall, scientists have a responsibility to work with the media to deliver the ‘right’ science to the public and make sure it reaches them in a timely fashion.

    Sandhya is a scientist, entrepreneur, serendipitous journalist and a manager. She lives in Singapore currently and wears many hats – Research Fellow at SBIC, A*STAR transitioning to a Programme and Grants Management role; Co-founder & Author, Biotechin.Asia, Biotech Media Pte. Ltd.; and a mother of a very active and inquisitive toddler! On top of all this, she just launched another startup and web platform to help scientists and students all over the world, called SciGlo. She is also the former Vice President & Publicity Chair of the A*STAR Postdoc Society (A*PECSS).

  • Cleaning up chemistry

    Tags: Green chemistry

    Russell Hewitt

    Scientist II

    Institute of Chemical and Engineering Sciences (ICES)

    ICES was established as an autonomous national research institute under A*STAR on October 1st 2002. ICES has established world leading laboratories, pilot facilities, and the necessary infrastructure to carry out a world class research programme in chemistry and chemical engineering sciences.

    Chemical manufacturing is a huge industry that delivers much needed chemicals to a variety of industries. Almost all of the everyday things we buy or use have been made in part with man-made chemicals. Laws and regulations strictly control the use of chemicals to ensure that the chemicals we are exposed to are not harmful to consumers.

    Chemists want to make the chemicals cheaply, but the manufacturing process should still be safe. This is important, not just for worker safety, but also for the environment and for the public who could suffer due to accidents at chemical plants.

    News of chemical spills or explosions make for very scary reading. The latest most widely publicized one was the Tianjin explosions in 2015, which were started by chemicals that most chemists definitely wouldn’t want to work with, such as the explosive nitrocellulose. But this is not an isolated case — there have been many instances of huge explosions or severe accidents occurring at chemical plants or storage facilities. The Bhopal disaster, for example, which was caused by the release of a highly toxic chemical used to manufacture an insecticide, is regarded as the worst industrial accident of all time.

    Chemists can learn from these horrible stories, however, and try to clean up our operations. For example, we learned that by redesigning the synthesis process the toxic chemical that caused the Bhopal disaster could have been avoided. Thus by changing the reactions we set into motion, we can improve our processes, making safer chemicals in a safe way.

    So how do we do this? When chemists first design a synthetic process we often go for the ‘tried and true’ methods, which typically use more potent chemicals that are often explosive, very toxic and highly flammable — so we need to be really careful when carrying out the process! With a little work however, many of these chemicals can be replaced with milder choices. We try to make the whole process safer both for the people doing the work and for the environment — this is called green chemistry. If a chemical product is manufactured using green chemistry practices, a scenario such as the Bhopal disaster should not occur.

    The great thing is, greener is often cheaper! Removing harmful chemicals means you cut costs associated with safety precautions. By careful design, we also can reduce the amounts of chemicals we use, cutting cost even more! As a result, green chemistry is now a huge focus for chemical manufacturing.

    The biggest impact we can make to improve our processes in this manner is in solvent reduction. Chemists use solvents to dissolve our chemicals so we can make sure they mix and react together well, but we often use much more than we need. It is important to both reduce our consumption of these solvents and to remove the worse solvents in a process. Historically, diethyl ether, an explosive and extremely flammable solvent, was used for anesthesia — until doctors tired of explosions at the operating table and the resulting fatalities. Dichloromethane, a potent environmental polluter, is another solvent of concern, especially due to its high volatility. It is often used in paint thinners, but despite its relatively low toxicity, it has caused over 50 deaths since 1980 in the US alone. Because of these hazards, these solvents and others are either banned or are in the process of being phased out in drug manufacturing. In fact, the pharmaceutical industry is actually the front runner in this movement, with many voluntarily banning or reducing the use of harmful solvents.

    Chemists are now trying to make our processes green as early as possible both to improve throughput and hasten the development toward commercial production. Ultimately this delivers the chemicals we need, in quantities that we can use, with a holistic view on safety for workers, the public and the environment.

    Dr Russell Hewitt is an organic chemist whose work covers carbohydrates, green chemistry and scale-up. He obtained his PhD from Victoria University of Wellington, New Zealand in 2010.