A minefield of data issues?

Even creating a small amount of data for my Masters project has brought home to me some of the issues around data – how to store it, where to store it, in what format to store it, how to ensure the appropriate people have access to it, how to stop people accessing it if they shouldn’t have access to it, how to future proof the storage, how to ensure the data and method used to collect it remain linked, who gets to keep it.

And that’s just for a few small plant biology experiments for my Masters. I’m sure there are many more levels of complexity for confidential data and big data. Some of these issue were discussed briefly with my Masters cohort, but it seems like that short conversation was only scratching the surface. I’m sure that as a (very) early career researcher there are a lot of things I don’t know and even more things I’m not even aware that I need to know.

 

Brightfield microscope image of Australian wild cotton (G. australe) leaf cross-section – one of the types of data from my Masters project (Photo: Belinda Fabian)

During my research break between my Masters and my PhD I’m working on up-skilling in a variety of areas; some directly related to my potential research topic(s), some which are generally related to study and/or my career (e.g. learning to code and using R) and others that just broaden my horizons (both scientifically and personally). One of the general study/career areas I’m learning about is data management through the 23 [research data] things program (see below for more information).

I see the 23 [research data] things program as helping me with generic study/career knowledge and skills and ideally it will will form part of a firm footing for me as a researcher. Awareness of the issues related to data management is important for researchers (and keeping digital data adds more concerns), but from my experience an understanding of it comes in a very piecemeal fashion during research training (as with many other things). So hopefully participating in this program will help me get out in front of the curve and make me aware of issues, solutions and strategies for managing data and where to find information down the track when the need becomes pressing.

Things you need to know:

The 23 [research data] things is a program run through ANDS (Australian National Data Service). More information can be found here. There’s an introductory webinar on tomorrow 1 March, 12.30-1.30 AEDT.

The program is free and runs from March to November 2016 (I know that sounds like a lot, but the FAQs suggest that it will only take about an hour a week and there will be breaks and catch-up opportunities during the year).

The program is advertised as being of interest to lots of different types of people – from the 23 [research data] things website: “If you are a person who cares for, and about, research data and want to fill in some gaps, learn more, find out what others are thinking… then this may be for you!” I’m getting involved as a research who will deal with data in my career, but if you’re a person who creates or cares for data then the program may be of interest to you too.

There’s a Meetup group for discussing the activities and other thoughts about the program and search #23RDThings on Twitter for all the buzz.

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Google Scholar is Filled with Junk Science

An interesting commentary on the state of Google Scholar’s search results.

I haven’t personally experienced the junk science results in Google Scholar that this author discusses, but then again my current research may not be attractive for predatory publishers. I’m focusing on plant physiology and biochemistry, which may be less prone to junk science when compared with more controversial areas or topics.

But this problem is very important to keep at the front of your mind if you’re researching a new area and may not have the skills to evaluate the research and determine ‘good science’ from ‘bad science’.

Drought vs Deluge – How Will Grasslands Cope with Climate Change?

Climate change due to human activities is predicted to change many aspects of the environment, from atmospheric carbon dioxide to temperature and rainfall1. Modellers are confident in the projected temperature increases, but the predictions about rainfall are much less certain. Changes in rainfall patterns will impact on many aspects of ecosystems, including how nutrients move.

Associate Professor Sally Power studies how these nutrient cycles are being affected by human-induced changes in the environment. She took up a position two years ago at the Hawkesbury Institute of the Environment, University of Western Sydney after completing her studies and working at the Imperial College in London. She previously completed a post-doctoral position at La Trobe University, Melbourne and loved Australia, so now she’s here permanently. Associate Professor Power is passionate about the understanding the interactive impact of multiple climate drivers on ecosystems.

At a recent seminar at Macquarie University Associate Professor Power spoke about three projects she is involved with at the moment:

  1. Drought and diversity in the UK (DIRECT)
  2. Rainfall extremes (DRI-grass)
  3. Elevated CO2 impacts on forest nutrient cycling (EucFACE)

The DIRECT project (Diversity, Rainfall and Elemental Cycling in a Terrestrial Ecosystem) aims to answer questions about how grassland ecosystems will respond to predicted rainfall changes and whether biodiversity will buffer these effects of a rainfall pattern change2. To test these ideas the research team constructed an array of grassland plots with a range of plants functional groups – perennials, caespitose grasses and annual plants (Figure 1)3.

Figure 1. Plant traits selected for the DIRECT experiment Image: Grantham Institute, Imperial College London (4).

Figure 1. Plant traits selection for the DIRECT experiment
Image: Grantham Institute, Imperial College London (4).

Rainfall predicted for the year 2100 (down 30% in summer, up 15% in winter) was applied to these plots to see how different vegetation communities might respond to rainfall changes2. Key ecosystem processes (such as respiration rate and nutrient cycling) were faster when there were a range of perennial plants present. Process rates in vegetation plots dominated by annual plants or caespitose grasses were not strongly affected by changes in rainfall2. This research showed that plant functional groups are important for maintaining grassland ecosystem function and they need to be considered in future management plans2.

In addition, the researchers used different plots in the same area and changed the rainfall pattern to see if drought and deluge impact differently on the grassland ecosystem. The rainfall treatments used were5:

  • Current levels;
  • Prolonged drought – 30% drop in rainfall; and
  • Reduced frequency – same amount of rain, concentrated into heavier falls less frequently.

The key findings were that changing the frequency of rainfall affected the number of species, especially the perennial species5. Surprisingly the number of species was not affected by the change in the total amount of rain (prolonged drought). The reduced rainfall frequency also lead to an increase in respiration and the grassland ecosystem switched from being a net carbon sink to net carbon source (from overall absorbing carbon to overall emitting carbon; Figure 2)5. The results of this experiment suggest that grassland ecosystems are relatively resistant to predicted rainfall changes5.

Figure 2. Change from carbon sink to carbon source for each of the  rainfall treatments (A = ambient; PD = prolonged drought; RF = reduced frequency). (Adapted from image presented by Associate Professor Sally Power)

Figure 2. Change from carbon sink to carbon source for each rainfall treatment (A = ambient; PD = prolonged drought; RF = reduced frequency; adapted from image presented by Associate Professor Power)

Associate Professor Power is also in the preliminary stages of some large scale experiments in western Sydney. The first of these experiments is DRI-grass (Drought & Root Herbivore Interactions in a Grassland Ecosystem). This study asks whether Australian grassland ecosystems have stronger responses to the amount or frequency of rain and whether these responses are affected by root herbivores6. Associate Professor Power emphasised that root herbivores are very abundant and their weight can exceed the weight of the sheep in a hectare7. Root herbivores can respond directly and indirectly to changes in rainfall patterns and can make it harder for plants to cope with climate change impacts8.

The research team has set up five different rainfall treatments: +50% rain; -50% rain; 3 week rainfall cycle with the same total amount of rain; summer drought; and the ambient conditions (Figure 3). The rainfall treatments only began in June 2013 and the root herbivores are not yet in place. So far the researchers have observed there are lower species abundances under drought conditions and an increase in summer rain has led to the dominance of African lovegrass.

Figure 3. Rainfall shelters for the DRI-grass experiment in the foothills  of the Blue Mountains (Image: The Hermon Slade Foundation; 6)

Figure 3. Rainfall shelters for the DRI-grass experiment in the foothills
of the Blue Mountains (Image: The Hermon Slade Foundation; 6)

The second project in western Sydney is being conducted in the EucFACE facility (Eucalyptus Free Air CO2 Enrichment)9 located in an intact Cumberland Plain Woodland ecosystem. Associate Professor Power and her team are looking at how elevated CO2 increases rates of nutrient cycling in the ecosystem. So far they have noticed there is an increase in available phosphorus, but no change in the amount of available nitrogen in elevated CO2 conditions.

Once the data is collected from these long term experiments, Associate Professor Power aims to understand some of the impacts of climate change on grassland ecosystems and make recommendations about how these systems should be managed to mitigate these impacts.

 

Learn more:

  1. IPCC (2013). Summary for Policymakers. In: Climate Change 2013: The Physical Science Basis. Working Group I Contribution to the IPCC Fifth Assessment Report. Cambridge University Press, Cambridge.
  2. Fry EL, Manning P, Allen DGP, Hurst A, Everwand G, Rimmler M & Power SA (2013). Plant Functional Group Composition Modifies the Effects of Precipitation Change on Grassland Ecosystem Function. PLoS ONE, 8(2): e57027. doi: 10.1371/journal.pone.0057027.
  3. Fry EL, Power SA & Manning P (2014b). Trait-based classification and manipulation of plant functional groups for biodiversity-ecosystem function experiments. Journal of Vegetation Science, 25, 248–261. doi: 10.1111/jvs.12068.
  4. Fry E, Hurst A, Everwand G, Rimmler M, Manning P & Power S (2009). Poster: “Diversity, Rainfall and Elemental Cycling in a Terrestrial ecosystem, (DIRECT)” presented at Committee for Atmospheric Pollution Effects Research AGM. https://workspace.imperial.ac.uk/climatechange/public/pdfs/CAPER_poster.pdf, accessed 25 May 2014.
  5. Fry EL, Manning P & Power SA (2014a). Ecosystem functions are resistant to extreme changes to rainfall regimes in a mesotrophic grassland. Plant Soil, doi: 10.1007/s11104-014-2137-2.
  6. The Hermon Slade Foundation (2014). Drought, deluge and diversity decline – How do root herbivores affect grassland resilience to predicted changes in rainfall patterns? http://www.hermonslade.org.au/projects/HSF_13_12/hsf_13_12.html, accessed 25 May 2014.
  7. Britton E (1978). A revision of the Australian chafers (Coleoptera: Scarabaeidae: Melolonthinae) Vol. 2. Tribe Melolonthini. Australian Journal of Zoology, 26, 1–150, Supplementary Series.
  8. Bardgett RD & Wardle DA (2003). Herbivore-mediated linkages between aboveground and belowground communities. Ecology, 84, 2258-2268. doi: 10.1890/02-0274.
  9. Hawkesbury Institute of the Environment (2014). EucFACE, http://www.uws.edu.au/hie/facilities/face, accessed 25 May 2014.

Synaesthesia – a ‘mixing of the senses’

The 2014 winner of the Paul Bourke Award was Associate Professor Anina Rich, a researcher from Macquarie University. This honour is awarded annually by the Academy of the Social Sciences in Australia to an early researcher who has achieved excellence in their field. As part of the award the winner presents their recent research in a public lecture at their home university. Dr Anina Rich studies how the brain integrates sensory information, particularly focusing on synaesthesia.

People with synaesthesia (synaesthetes) perceive sensory information in a different way. They can experience colours in association with letters, sounds or smells. The most common type of synaesthesia is letter-colour (Figure 1) but there are also other types such as auditory-visual and olfactory-visual synaesthesia. Chiou & Rich (2014) define synaesthesia as a ‘concurrent and distinct experience in a separate or the same modality’.

Figure 1. A representation of the colours one synaesthetes associates with each letter and number.

Figure 1. A representation of the colours one synaesthete associates with each letter and number.

Synaesthesia is present is 0.05-4% of the population and may have a genetic link. Relatives with synaesthesia are common and it is more prevalent in females than males. Many people don’t realise they are a synaesthete as their synaesthetic experience is constant over time and normal for them (perception in general is subjective).

Dr Rich is interested in studying synaesthesia as it may provide information about how information is normally integrated. Synaesthesia is not a medical disorder, there are no deficits associated with it. Many synaesthetes report that the extra sensory information they receive can be used to improve their memory and learning. Dr Rich is interested in seeing if synaesthetes have extra connections in the brain or are just using their connections between brain sections in a different way to the rest of the population.

To test this idea, Dr Rich and her team asked seven auditory-visual synaesthetes to describe the location on a grid of colours and shapes in response to auditory stimulus (Figure 2). Using functional MRI, Dr Rich and her team were able to work out that the occipital lobe in the back of the brain is stimulated when auditory-visual synaesthetes are presented with auditory information.

Figure 2. Examples of the stimuli presented to the auditory-visual synaesthetes (Chiou et al. 2013).

Figure 2. Examples of the stimuli presented to the auditory-visual synaesthetes (Chiou et al. 2013).

In addition, Dr Rich’s team has been investigating the areas of the brain non-synaesthetes use to process information about objects and colours. For example, a lemon is instantly recognisable as a lemon due to its yellow colour. When this colour is changed to something incongruent, like a red lemon, it becomes harder to identify. This object-colour binding is centralised in the anterior temporal lobe of the brain. Dr Rich is now conducting research to see if the same brain location of object-colour binding is seen in synaesthetes and what happens to their synaesthetic experience if the activity of this brain region is temporarily disrupted (Chiou et al. 2014).

Studying synaesthesia and how the brain processes sensory information is important as it can provide information about how learning and experience can alter our perception. As Dr Rich said in her presentation “what we already know has huge influence on what we think we see”. This work has implications for designing environments where people are required to process multiple sources of information, such as airplane cockpits.

To learn more:

Chiou R & Rich AN (2014). The role of conceptual knowledge in understanding synaesthesia: Evaluating contemporary findings from a “hub-and-spokes” perspective. Frontiers in Psychology, 5(105), 2-18. doi:  10.3389/fpsyg.2014.00105.

Chiou R, Stelter M & Rich AN (2013). Beyond colour perception: Auditory-visual synaesthesia induces experiences of geometric objects in specific locations. Cortex, 49(6), 1750-1763.

Chiou R, Sowman PF, Etchell AC & Rich AN (2014).A Conceptual Lemon: Theta Burst Stimulation to the Left Anterior Temporal Lobe Untangles Object Representation and Its Canonical Color. Journal of Cognitive Neuroscience, 26(5) 1066-1074. doi:10.1162/jocn_a_00536.

Prevention is Better Than Cure – Keeping Dementia at Bay

What do we know about dementia?

Recently Associate Professor Michael Valenzuela spoke at Macquarie University’s Australian Advanced School of Medicine about his work with elderly Australians. Associate Professor Venezuela leads a team of researchers at the Brain and Mind Research Institute, part of the University of Sydney. His work is important for determining how elderly people can be productive into old age rather than being confined to institutions or nursing homes. Dementia is not one disease, but a collection of diseases characterised by a decline in brain functions, such as perception, memory, language and cognitive skills1. Research has shown that shrinkage of the hippocampus (a brain section important for memory and spatial skills) is an indicator for dementia (Figure 1)2.

Figure 1. Shrinkage of the hippocampus in healthy elderly people and suffers of  Alzheimer’s Disease (one of the diseases under the umbrella of dementia)2.

Figure 1. Shrinkage of the hippocampus in healthy elderly people and sufferers of Alzheimer’s Disease (one of the diseases under the umbrella of dementia)2.

What are the risk factors?

So what determines whether an elderly person can maintain an independent lifestyle or become dependent on others for care and support? A major risk factor for dementia is being mentally lazy. A person’s cognitive lifestyle across the years of their life is a major factor in the risk of cognitive decline and developing dementia as a person ages. A survey of elderly people in Australia, the UK, the USA and France (Lifetime of Experience Questionnaire) is currently being conducted to find out more about how cognitive lifestyle correlates with risk of dementia3.

One recent finding of the Lifetime of Experience Questionnaire is that managerial experience during a person’s working life is correlated to a bigger hippocampus. Managing at least 10 people can be effective at preventing the onset of dementia4. The researchers analysing the data have postulated that interactions with people and the complex skill set required to successfully perform in a management position are what leads to this reduction in dementia risk.

What can we do to stave off the onset of dementia?

The findings from Associate Professor Valenzuela’s research show that one way to reduce the risk of dementia is to maintain an active cognitive lifestyle (ACL)5. Consistently ‘working out’ your brain can increase the time you live with a clear mind and reduce the amount of time living with dementia6. This pushing back of the onset of dementia is known as compression of cognitive morbidity. Pablo Picasso is a wonderful example of a person who was active and independent into old age. He continued to paint right up to his death at 73 years old (Figure 2).

Figure 2. Pablo Picasso adding paint to an artwork.

Figure 2. Pablo Picasso adding paint to an artwork.

How do we go about promoting active cognitive lifestyles in communities?

Associate Professor Valenzuela’s team has started a Brain Training Lab at the Montefiore Home in Randwick, Sydney (Figure 3). Here the program participants undergo computer-assisted cognitive training for 60 minutes, three times a week over a 12 week program. There are two groups – one does repeated standardized tasks and the other group watches National Geographic videos and answers questions about them. This study aims to answer questions about the minimum/maximum amount of training required to improve cognitive function and how long positive effects from brain training can last7.

Figure 3. Participants undertaking computerised tasks as part of the Brain Training Lab.

Figure 3. Participants undertaking computerised tasks as part of the Brain Training Lab.

Another experiment that has been established is the Study of Mental Activity and Regular Training (SMART) trial. This study combines mental and physical training to see if either type of training in isolation or the combination of both improves cognitive abilities8. The link between exercise and brain health has been observed in rat experiments. Exercise has been shown to improve brain organisation and object/place recognition in aged rats. This link has also been demonstrated in humans; exercise training has been shown to increase the size of the hippocampus9. The SMART study includes 100 Sydneysiders over the age of 55 and they conduct training twice a week for six months. Measurements of cognitive ability before any training, after six months of training and at an 18 month follow-up hope to determine if there are improvements in the brain, general health and quality of life of the participants8.

Wider implications

Only in the past 100 years have people been able to live beyond 65 years of age. The population of the world is aging fast due to the maturing of the baby boomer generation and medical advancements extending life expectancy. The combination of aging populations and increased life expectancy means more people than ever before are soon going to be retired. Retirement design needs to be carefully considered so the development of dementia in aging population doesn’t negatively impact on the economy and health care systems10. Studies on aging and cognitive ability have shown that it isn’t effective to retire and then do no ‘brain work’ for 20-30 years. Associate Professor Valenzuela warns that retirement design needs to take this into account. Opportunities need to be created where elderly people can replace the intensive cognitive and social interactions of a work environment when they retire. Only in this way can the older people retain their cognitive abilities and stave off the onset of dementia.

Want to learn more?

  1. Department of Health, Commonwealth of Australia (2013). Dementia, http://www.health.gov.au/dementia, accessed 23 May 2014.
  2. Thompson PM, Hayashi KM, de Zubicaray GI, Janke AL, Rose SE, et al. (2004). Mapping hippocampal and ventricular change in Alzheimer disease. NeuroImage, 22(4), 1754-1766. doi: 10.1016/j.neuroimage.2004.03.040.
  3. Valenzuela M & Sachdev P (2007). Assessment of Complex Mental Activity Across the Lifespan: Development of the Lifetime of Experiences Questionnaire. Psychological Medicine, 37, 1015-1026. doi: 10.1017/S003329170600938X.
  4. Suo C, Leon I, Brodaty H, Trollor J, Wen W, et al. (2012). Supervisory experience at work is linked to low rate of hippocampal atrophy in late life. NeuroImage, 63, 1542-1551. doi: 10.1016/j.neuroimage.2012.08.015.
  5. Marioni RE, van den Hout A, Valenzuela MJ, Brayne C, Matthews FE, et al. (2012). Active cognitive lifestyle associates with cognitive recovery and a reduced risk of cognitive decline. J Alzheimers Dis, 28(1), 223-230. doi: 10.3233/JAD-2011-110377.
  6. Marioni RE, Valenzuela MJ, van den Hout A, Brayne C, Matthews FE (2012).Active Cognitive Lifestyle Is Associated with Positive Cognitive Health Transitions and Compression of Morbidity from Age Sixty-Five.PLoS ONE, 7(12), e50940.doi: 10.1371/journal.pone.0050940.
  7. Lampit A, Suo C, Gates N, Kwok SSY, Naismith S et al. (2011). Temporal evolution of cognitive training-induced structural and functional brain plasticity. 10th National Emerging Researchers in Ageing Conference, University of New South Wales, Sydney. http://rng.org.au/timecourse/, Accessed 23 May 2014.
  8. Gates NJ, Valenzuela M, Sachdev PS, Singh NA, Baune BT, et al. (2011) Study of Mental Activity and Regular Training (SMART) in at risk individuals: A randomised double blind, sham controlled, longitudinal trial. BMC Geriatrics, 11(19), doi: 10.1186/1471-2318-11-19.
  9. Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, et al. (2011). Exercise training increases size of hippocampus and improves memory. Proceedings of the National Academy of Sciences of the United States of America, 108(7), 3017-3022. doi: 10.1073/pnas.1015950108.
  10. Brookmeyer R, Johnson E, Ziegler-Graham K & Arrighi HM (2007). Forecasting the global burden of Alzheimer’s disease. Alzheimer’s & Dementia, 3(3), 186–191. doi: 10.1016/j.jalz.2007.04.381.

A new direction in HIV therapy

HIV is a worldwide problem – 35.3 million people are living with HIV or AIDS and 36 million people have died from AIDS related illnesses1. As the HIV/AIDS epidemic is such a big problem, there are many agencies working hard to come up with effective and efficient treatments. In a recent seminar at Macquarie University’s Australian School of Advanced Medicine, Professor Anthony Kelleher discussed the cutting edge HIV research his team has been conducting. His research at The Kirby Institute, University of NSW, focuses on how HIV reservoirs are established and maintained and how this information can help to develop a cure.

Currently, the only option for HIV treatment is the use of antiviral therapy. This treatment suppresses the replication of HIV virus particles by targeting different stages of the virus lifecycle, such as the entry of the virus particles into the cell, creation of DNA from virus RNA, insertion of the virus DNA into the cell’s nuclear DNA or preventing mature virus particles from leaving the cell (Figure 1)2.

Figure 1. Anti-viral drugs target different stages of the HIV lifecycle.

Figure 1. Anti-viral drugs target different stages of the HIV lifecycle.

Antiviral therapies work well, but they don’t eliminate the virus from the body3. As soon as patients stop anti-viral drug treatment, HIV levels can rapidly rise due to the stockpile of virus particles lurking in cells (the viral reservoir)4. This means patients with HIV need anti-viral drugs for the rest of their lives, otherwise the virus will return with vigor and the patient will relapse (Figure 2).

Figure 2. HIV+ patients currently take a cocktail of drugs to suppress the virus.

Figure 2. HIV+ patients currently take a cocktail of drugs to suppress the virus.

Staying on anti-viral drugs for a lifetime can have a lot of unwanted side effects, such as metabolic diseases and osteoporosis5. There are research teams developing a vaccine for HIV, but this is still in phase 1 of clinical trials (preliminary safety tests). A vaccine needs multiple rounds of trials and will take approximately 15 years before it can be used in the general population6.

Only one person has been cured of HIV – a patient with HIV developed an additional disease which required a bone marrow transplant. The bone marrow donor had a deletion of his CCR5 gene, a receptor for HIV. As the HIV receptor was no longer present the HIV could no longer bind and the patient was cured4. Unfortunately, a bone marrow transplant from a donor with a CCR5 gene deletion is not an option for everyone with HIV, so other avenues are being explored.

Professor Kelleher and his team are interested in developing alternatives to long-term medications and are looking at the genes of HIV and the immune system for a possible solution. The team has just recently received ethics clearance to start human clinical trials using siRNAs (small interfering RNAs) to degrade the CCR5 gene receptor for HIV. This method aims to stop expression of the HIV genes (silencing) which stops the virus particles from replicating7 (Figure 3). This will remove the viral reservoir, but the genes will still be present in the patient’s genome. This method has been effective for other viruses, such as the Human Papilloma Virus, Polio, Hepatitis B and Hepatitis C, and oncogenes have also been silenced using this method8,9.

The way retroviruses, such as HIV, replicate is by inserting their genetic material into the host cell’s genome and taking over the DNA replication machinery to produce messenger RNA and then proteins. The siRNAs can bind to the HIV messenger RNAs (Figure 3) and degrade them, stopping the creation of the proteins that create HIV particles10. Alternatively the siRNAs can bind to the DNA and change the chemical structure so the HIV genes can’t be transcribed4. The siRNAs are so specifically targeted to HIV strains that there is no chance of detrimental impacts on other genes10.

Figure 3. siRNAs degrade messenger RNA so it can’t be translated into protein (McManus & Sharp 2002).

Figure 3. siRNAs degrade messenger RNA so it can’t be translated into protein (McManus & Sharp 2002).

Another research group has shown that treatment with siRNAs works to silence an HIV-type virus in mice11 so the next step is to try this method with human HIV. Professor Kelleher’s team will start the treatment with a small group of HIV patients, following these steps:

  1. Identify HIV+ patients currently taking anti-viral drugs to suppress the virus;
  2. Treat with siRNA therapy;
  3. Stop anti-viral treatment; and
  4. Monitor the patients to see if the HIV stays suppressed.

If the HIV symptoms don’t return then the siRNAs have eliminated the viral reservoir and silenced the HIV. The siRNA treatment has been shown to be effective in human cells for up to 30 days in a laboratory setting. If the same is shown in human clinical trials, this could lead to a significant improvement for the quality of life for millions of HIV+ patients in the future.

Want to know more?

  1. World Health Organisation (2014.) HIV/AIDS, http://www.who.int/gho/hiv/en/, accessed 22 May 2014.
  2. Mehellou Y & De Clercq E (2010). Twenty-Six Years of Anti-HIV Drug Discovery: Where Do We Stand and Where Do We Go? Journal of Medicinal Chemistry, 53(2), 521-538. doi: 10.1021/jm900492g.
  3. Suzuki K, Marks K, Symonds G, Cooper DA, Kelleher AD, et al. (2013). Promoter targeting shRNA suppresses HIV-1 infection in vivo through transcriptional gene silencing. Molecular Therapy – Nucleic Acids, 2, e137; doi: 10.1038/mtna.2013.64.
  4. Kent SJ, Reece JC, Petravic J, Martyushev A, Kramski M, et al. (2013). The search for an HIV cure: tackling latent infection. The Lancet, 13(7), 614-621. doi: 10.1016/S1473-3099(13)70043-4.
  5. Grund BA, Peng GA, Gibert CLB, Hoy JFC, Isaksson RLA, et al. (2009). Continuous antiretroviral therapy decreases bone mineral density. AIDS, 23(12), 1519-1529. doi: 10.1097/QAD.0b013e32832c1792.
  6. National Health and Medical Research Council, Commonwealth of Australia (2014). Australian Clinical Trials. http://www.australianclinicaltrials.gov.au/node/5, accessed 22 May 2014.
  7. McManus MT and Sharp PA (2002). Gene silencing in mammals by small interfering RNAs. Nature Reviews Genetics, 3, 737-747. doi: 10.1038/nrg908.
  8. Saleh MC, Van Rij RP, Andino R (2004). RNA silencing in viral infections: insights from poliovirus. Virus Research, 102, 11–17. doi: 10.1016/j.virusres.2004.01.010.
  9. Li S-D, Chono S & Huang L (2008). Efficient Oncogene Silencing and Metastasis Inhibition via Systemic Delivery of siRNA. Molecular Therapy, 16(5), 942-946. doi: 10.1038/mt.2008.51.
  10. Suzuki, K, Ishida T, Yamagishi M, Ahlenstiel C, Swaminathan S, et al. (2011). Transcriptional gene silencing of HIV-1 through promoter targeted RNA is highly specific. RNA Biology, 8(6), 1035-1046. doi: 10.4161/rna.8.6.16264.
  11. Mitsuyasu RT, Merigan TC, Carr A, Zack JA, Winters MA, et al. (2009). Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells. Nature Medicine, 15, 285-292. doi: 10.1038/nm.1932.

Going a bit batty – How do bats withstand so many viruses?

Dr Michelle Baker from the CSIRO Australian Animal Health Laboratory spoke at Macquarie University last week about her work on bat immune systems. Her lab recently contributed to the high impact Hendra virus vaccine for horses. Dr Baker’s work has implications for disease control and prevention and management of virus spillovers into human communities worldwide.

Bats make up 20% of mammalian diversity, are long lived for their body size and are the only mammals with powered flight. Bats are vital to ecosystem functions such as pollination, fertilisation and insect control (Calisher et al. 2006). Despite these unique characteristics they are not intensively studied like most other mammal groups. Before Dr Baker’s research group focused on bats not much was known about their immune systems (Baker et al. 2013).

Figure 1. Possible virus transmission routes from bats to humans. (adapted from image presented by Dr Michelle Baker)

Figure 1. Possible virus transmission routes
(adapted from image presented by Dr Michelle Baker).

Bats act as viral reservoirs, meaning they carry a range of viruses (He et al. 2010; Ng & Baker 2013). Fatal human viruses that can be traced back to bats include Rabies, Hendra, Ebola, Marburg and the SARS coronavirus (Ng & Baker 2013). These viruses occasionally spill over from bats into other animals and that’s normally how humans become infected (Figure 1). But even with this load of up to 100 different viruses, bats are hardly ever sick (Baker et al. 2013).

The bat’s lack of symptoms from viral infections was puzzling, so Dr Baker’s team looked more closely at bat immune systems. When a viral infection occurs in other mammals the immune system quickly delivers a generic response (innate response) and then a specific response occurs more slowly (adaptive response; Katze et al. 2002). The researchers observed that bats don’t develop many antibodies in response to infections, so they thought the bat immune system might be knocking down the viruses before the immune system could mount an adaptive response (Baker et al. 2013).

Figure 2. The Black Flying Fox, Pteropus alecto.

Figure 2. The Black Flying Fox, Pteropus alecto.

To test this idea the researchers sequenced the genomes and studied the immune responses of two species of bat: Myotis davidii, a micro bat, and Pteropus alecto, a megabat (Figure 2). They found the collection of immune genes in bats is different to other mammals. For example, bats have fewer genes for interferon production (Papenfuss et al. 2012).

Interferon is a protein produced by the immune system in response to the detection of viral invaders. It starts a signaling cascade that creates an anti-viral state in cells (He et al. 2010; Figure 3). High interferon levels can be toxic for cells, so normally the interferon level is very low. When a viral infection is detected, the interferon level is dramatically increased which signals cells to start fighting the infection (Katze et al. 2002). There are multiple types of interferon, but the type Dr Baker spoke most about is interferon alpha (IFNA).

Figure 3. Interferon signaling cascade - causes expression of immune system genes and creates an antiviral state in cells (Katze et al. 2002).

Figure 3. Interferon signaling cascade – causes expression of immune system genes and creates an antiviral state in cells (Katze et al. 2002).

In contrast to expectations, bat cells were found to have their IFNA genes constantly switched on and there is no increase when cells are infected with viruses (Figure 4). Even with this high IFNA level the toxicity effect observed in other mammals isn’t seen in bats. This IFNA level in bats may be part of the reason they can carry so many viruses, but don’t often get sick from them. Other research groups have found that bat IFNA genes have been positively selected which means they must have been beneficial to bats as they lived with viruses in the past (Calisher et al. 2006; He et al. 2010). Recent work has hypothesised that there is a link between the evolution of flight and the ability of bats to harbor viruses without becoming sick (Zhang et al. 2013; O’Shea et al. 2014).

These findings were very new and unexpected so there were lots of questions from the audience after the seminar. It seems like everywhere Dr Baker turned there were more questions! These are the ‘top 5’ questions asked:

  1. Why aren’t the bats harmed by high levels of interferon in uninfected cells like other mammals?
  2. What triggers the spillover of viruses into other animals that cause outbreaks?
  3. Could there be a link between the interferon level and their long lifespan relative to their body size?
  4. What is the bat immune response to bacterial infection?
  5. Why doesn’t the bat immune response completely wipe out the viruses? How come the viruses can persist and then spill over into other animals?
Figure 4. Interferon alpha levels in infected and uninfected cells in bats and other mammals  (adapted from image presented by Dr Michelle Baker).

Figure 4. Interferon alpha levels in infected and
uninfected cells in bats and other mammals
(adapted from image by Dr Michelle Baker).

So much is currently unknown about how bats can carry so many viruses without being sick. Dr Baker and her team are working to find answers to these questions and more. As human populations increasingly overlap with bat habitats there is more chance of spillover events affecting human and animal populations. Dr Baker’s research could be used to understand human responses to viruses and develop anti-viral treatments in the future.

Learn more:

Baker ML, Schountz T & Wang L-F (2013). Antiviral Immune Responses of Bats: A Review. Zoonoses and Public Health, 60, 104-116. doi: 10.1111/j.1863-2378.2012.01528.x

Calisher CH, Childs JE, Field HE, Holmes KV & Schountz T (2006). Bats: Important Reservoir Hosts of Emerging Viruses. Clinical Microbiology Reviews, 19(3), 531-545. doi:  10.1128/CMR.00017-06

He G, He B, Racey PA & Cui J (2010). Positive Selection of the Bat Interferon Alpha Gene Family. Biochemical Genetics, 48(9-10), 840-846. doi: 10.1007/s10528-010-9365-9

Katze M, He Y & Gale M (2002). Viruses and interferon: A fight for supremacy. Nature Reviews Immunology, 2(9), 675-687. doi: 10.1038/nri888

Ng J & Baker ML (2013). Bats and bat-borne diseases: a perspective on Australian megabats. Australian Journal of Zoology, 61, 48-57. doi: 10.1071/ZO12126

O’Shea T, Cryan P, Cunningham A, Fooks A, Hayman D, Luis A, Peel A, Plowright R, & Wood J (2014). Bat Flight and Zoonotic Viruses. Emerging Infectious Diseases, 20(5), 741-745. doi: 10.3201/eid2005.130539

Papenfuss AT, Baker ML, Feng Z-P, Tachedjian M, Crameri G, Cowled C, Ng J, Janardhana V, Field HE, Wang L-F (2012). The immune gene repertoire of an important viral reservoir, the Australian black flying fox. BMC Genomics, 13:261, doi: 10.1186/1471-2164-13-261.

Zhang G, Cowled C, Shi Z, Huang Z, Bishop-Lilly KA, Fang X, Wynne JW, Xiong Z, Baker ML, Zhao W, Tachedjian M, Zhu Y, Zhou P, Jiang X, Ng J, Yang L, Wu L, Xiao J, Feng Y, Chen Y, Sun X, Zhang Y, Marsh GA, Crameri G, Broder CC, Frey KG, Wang L-F & Wang J (2013). Comparative Analysis of Bat Genomes Provides Insight into the Evolution of Flight and Immunity. Science, 339, 456-460. doi: 10.1126/science.1230835

Silhouette images in Figure 1 sourced from: horse, bat, pig, humans.