tag:theconversation.com,2011:/africa/topics/cell-growth-419/articlesCell growth – The Conversation2020-12-11T18:01:17Ztag:theconversation.com,2011:article/1508072020-12-11T18:01:17Z2020-12-11T18:01:17ZAI technique that predicts cell growth could someday diagnose cancer or develop new drugs<figure><img src="https://images.theconversation.com/files/374402/original/file-20201211-19-irkxhy.jpg?ixlib=rb-1.1.0&rect=0%2C77%2C4000%2C1868&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Our AI made its predictions by looking at how cells changes and act under different conditions in the body.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-vector/doctors-researchers-using-innovative-technologies-medicine-1627208287">elenabsl/ Shutterstock</a></span></figcaption></figure><p>Machine learning technologies are everywhere. They’re used by search engines, social media, and even in online banking. But one area that this technology is still emerging is medicine. </p>
<p>Machine learning technologies could be very promising in medicine, and could be used for many applications, such as detecting signs of disease in cells, or discovering new drugs for rare diseases. But in order for a machine learning approach to be able to do such things, it needs to be both accurate and able to understand how cells work.</p>
<p>Our team has developed an <a href="https://www.pnas.org/content/117/31/18869">accurate machine learning approach</a> that can predict cell growth in a way that researchers can easily understand. The machine learning technique makes its predictions by looking at how cells change and act under different conditions. This method could someday be used to diagnose cancer, or predict how certain drugs may interact with a patient. </p>
<h2>Interpreting machine learning predictions</h2>
<p>In essence, machine learning is a form of artificial intelligence (AI) in which data is used to teach computers to make decisions on their own, without a person needing to be there to do it for them. </p>
<p>But one of the main weaknesses of machine learning techniques in biology and medicine is the fact that they don’t incorporate biological knowledge – such as underlying cell biochemistry – in the learning process. In general, they also ignore this knowledge when making their predictions. This is because these systems treat biological information as data or numbers, so they don’t consider the actual biological meaning of these numbers.</p>
<p>Such systems are often referred to as “black box” systems. These are AI that are fed data, and provide users with a clear decision or prediction based on the patterns found in that data. However, it’s usually unclear how the AI made its decision because of how complex its analysis is. </p>
<p>Black box predictions aren’t a major issue in fields where high accuracy is the most important goal – such as in software used to predict spam emails. But it’s a major disadvantage in biomedicine. Black box predictions can’t be interpreted by researchers because of <a href="https://theconversation.com/people-dont-trust-ai-heres-how-we-can-change-that-87129">how complex they are</a>, meaning they have little understanding of how the AI algorithm reaches its prediction. </p>
<p>“White box” systems, on the other hand, could be slightly less accurate in their decisions or predictions, but it’s clearer to users the relationships they’ve inferred based on the data given. The benefit of white box systems is that users can understand what information the system used to make its prediction, and because it’s understandable, users can also interrogate the decision itself and interpret it from a biological point of view.</p>
<p>Machine learning predictions need to be interpretable and justifiable to be trustworthy and to work in biomedicine. In the case of detecting cancer, if the AI technique made a false-positive prediction, it could lead to unnecessary treatment – while false-negative predictions could lead to the disease being left untreated. Understanding the predictions made by machine learning algorithms will also help avoid false negatives when researching potential drugs and any side effects they might have.</p>
<h2>Predicting cell growth</h2>
<p>In order for AI methods to work in biomedicine, we first needed to design a machine learning approach that could <a href="https://research.tees.ac.uk/ws/portalfiles/portal/16665230/PNAS_postprint.pdf">predict cell growth</a>, and understand what was driving this growth. Understanding how cells grow and how their growth changes in different conditions is the first step in being able to design an AI that can detect the presence of a disease or predict how well certain treatments may work.</p>
<p>Our team evaluated 27 different machine learning approaches that looked at both gene expression profiles and mechanistic metabolic models. Gene expression profiles showed how the cell’s process of assembling proteins changed under a variety of conditions. Metabolic models showed how the underlying cell biochemistry works in each strain.</p>
<p>We then built our own white box machine learning technique, which would allow us to easily interpret how the AI made its decision, overcoming the shortfalls of previous computer learning techniques. We did this by teaching our AI to make decisions using data from both gene expression and metabolic models – something that hasn’t been done before.</p>
<p>Using both models to build our machine learning approach improved predictive accuracy compared to using only gene expression data by up to 4% in some cases. This has the advantage of revealing previously unknown interactions between gene expression and metabolic activity.</p>
<figure class="align-center ">
<img alt="A petri dish of Saccharomyces cerevisiae yeast grown in the lab." src="https://images.theconversation.com/files/374403/original/file-20201211-14-11io229.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/374403/original/file-20201211-14-11io229.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/374403/original/file-20201211-14-11io229.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/374403/original/file-20201211-14-11io229.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/374403/original/file-20201211-14-11io229.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/374403/original/file-20201211-14-11io229.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/374403/original/file-20201211-14-11io229.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">This type of yeast is common in baking and brewing.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/saccharomyces-cerevisiae-366714533">sruilk/ Shutterstock</a></span>
</figcaption>
</figure>
<p>We then checked our approach on more than 1000 different strains of <em>Saccharomyces cerevisiae</em> – a species of yeast common in baking, brewing, and wine making. Data on this type of yeast is widely available, making it easy to evaluate the effectiveness of our machine learning approach.</p>
<p>The results from the yeast showed that with our white-box approach, we can maintain and in some cases improve the predictive accuracy of AI techniques. But importantly, we also offer an interpretation of these predictions, by explaining which biochemical reaction is active in the cell across various conditions.</p>
<p>Our approach incorporates information on biological mechanisms, such as cell biochemistry, in the learning process. This overcomes the black-box limitations of conventional data-driven approaches, and achieves a step towards the development of interpretable machine learning models.</p>
<p>The advantage of this is that machine learning models based on our approach will be more trustworthy. Our results show that combining data and knowledge-driven models gives researchers more information about how cells grow and work in certain conditions.</p>
<p>While this will still need to be tested using human cells, it could have many promising applications in the future. For example, understanding how cancer cells are influenced by their genetic make-up and by environmental conditions is a major and pressing challenge in treating and preventing it.</p><img src="https://counter.theconversation.com/content/150807/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Claudio Angione received funding from UKRI Biotechnology and Biological Sciences Research Council
(BBSRC). He was also supported by UKRI Research England’s THYME project.</span></em></p>Understanding how cells grow under a variety of conditions is necessary for diagnosing disease and developing treatments in the future.Claudio Angione, Reader, Computer Science, Teesside UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/288722014-07-07T16:02:22Z2014-07-07T16:02:22ZYour skin can ‘sniff’ certain aromas that help it heal faster<figure><img src="https://images.theconversation.com/files/53179/original/hwzd9bsz-1404735170.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Sandalwood: something in it?</span> <span class="attribution"><a class="source" href="http://commons.wikimedia.org/wiki/File:Burning_incense_sticks_in_Vietnam.jpg">Christopher Michel</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Humans have about 350 different types of olfactory receptors in the nose, which detect odours and start a signalling process that then messages the brain. These receptors work together to give us a sense of smell. But the nose is not the only place where olfactory receptors are found. Cells of other tissues of the body use these receptors to react to chemical “odour” compounds. And we’ve discovered that their presence in skin cells can accelerate wound healing.</p>
<p>Olfactory receptors <a href="http://www.ncbi.nlm.nih.gov/pubmed/12644552">have been shown</a> to exist in nearly all human tissues, but their function outside of detecting odours has only been demonstrated in a few cell types, <a href="http://archive.today/RoFRA">such as sperm</a>, <a href="http://www.ncbi.nlm.nih.gov/pubmed/18336002">prostate</a> and the <a href="http://www.ncbi.nlm.nih.gov/pubmed/15626907">colon</a>. </p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/53204/original/9wcn4mvj-1404748310.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/53204/original/9wcn4mvj-1404748310.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=440&fit=crop&dpr=1 600w, https://images.theconversation.com/files/53204/original/9wcn4mvj-1404748310.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=440&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/53204/original/9wcn4mvj-1404748310.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=440&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/53204/original/9wcn4mvj-1404748310.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=553&fit=crop&dpr=1 754w, https://images.theconversation.com/files/53204/original/9wcn4mvj-1404748310.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=553&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/53204/original/9wcn4mvj-1404748310.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=553&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Steering the right course.</span>
<span class="attribution"><a class="source" href="https://www.flickr.com/photos/sexyeggs/7118478595/in/photolist-9gwANP-4rQBiz-8XM3a-a6cdWw-6Mp2vu-u4b66-bR34Fz-61bQsq-6uieUZ-c2MUXf-c2MURU-c2MULJ-8w8Pts-8auzZc-4KtoE6-8FBYme-54oNsi-7SZYAo-2uZqG-8K4TVd-7jrQns-RNLTK-9CCMkt-621JMP-4wkwk8-8FC5jg-7Ct7vS-bR5Rr-a5mwVX-7pSEKb-5FFYLT-4y9Hcf-7ThvBr-8q4QzP-2fppWx-7R4taQ-5kHQV8-4UWkG9-qUqDH-5FnSqK-j6Fcph-6cF2wt-akqb2R-c2MV3h-8FC4mr-6rHPUd-FRner-ckxYcd-9CgwzH-cvJ3C">Sexy Eggs</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>For example, activation of the olfactory receptors in sperm influences its swimming direction and speed, while in colon cells it induces a <a href="http://www.nytimes.com/2005/08/24/health/24iht-snbrain.html?pagewanted=all&_r=0">release of serotonin</a> (a process that is part of the enteric nervous system – also nicknamed our “<a href="http://www.scientificamerican.com/article/gut-second-brain/">second brain</a>”). </p>
<p>In our study, <a href="http://dx.doi.org/10.1038/JID.2014.273">published in the Journal of Investigative Dermatology</a>, we discovered that olfactory receptors can also be found in keratinocytes – the cells that form the outermost layer of the skin – and that activating these receptors increases the rate of proliferation and migration of these skin cells.</p>
<p>We found that skin cells possess a receptor called OR2AT4 that responds to the scent of sandalwood, frequently used in incense sticks and perfumes. And we were able to activate this receptor using Sandalore, a synthetic sandalwood scent. Using samples that included cultured keratinocyte cells and human skin, we discovered that activating OR2AT4 triggered a signal pathway that led to a higher concentration of calcium in the cells. This in turn led to an increase in the proliferation and a quicker migration of keratinocytes – processes which typically facilitate wound healing. Scratching experiments on isolated human skin tissue confirmed this wound healing effect.</p>
<p>In addition to OR2AT4, we found a couple more members of the olfactory receptor family, not only in the keratinocytes skin cells but also in the melanocytes – the melanin-producing cells found in the bottom layer of the epidermis – and in fibroblasts cells, which also play a crucial role in the wound healing process. The function of these additional receptors is something that we are planning to characterise in future experiments. </p>
<p>The results so far show that these olfactory receptors in human skin have potential therapeutic benefits, and understanding the mechanism could be a possible starting point for new drugs and cosmetics. Sandalore, for example, could have potential use as a topical ointment that could have anti-ageing properties or accelerate wound healing.</p>
<p>But before this happens it’s worth remembering that concentrated fragrances should be handled with care until we have ascertained which functions the different types of olfactory receptors in skin cells have. Besides the positive effect of Sandalore on the receptor OR2AT4, we could well discover that other receptors elicit negative effects on human skin cells.</p><img src="https://counter.theconversation.com/content/28872/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Hanns Hatt does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Humans have about 350 different types of olfactory receptors in the nose, which detect odours and start a signalling process that then messages the brain. These receptors work together to give us a sense…Hanns Hatt, Professor of Cellphysiology, Ruhr University BochumLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/282252014-06-19T16:00:54Z2014-06-19T16:00:54ZSalamanders give clues to how we might regrow human limbs<figure><img src="https://images.theconversation.com/files/51664/original/kck5kqb7-1403176935.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Budding friends.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/anitagould/124121368/sizes/l/in/photolist-bY9XA-yBWeh-4uJntS-6S52-xZ2mN-faRduE-fvecH2-8hkLwv-ecw8gB-kxPHrv-d5FXa-7WATZA-4Awjh6-jz8Xpp-7vL4xn-5gf6RB-gKzkZS-4uuWVM-pjru7-n9NVjE-eMwZ5o-9y7PAy-4VvkQ8-fPMm4d-eMkzsT-5bYQxW-3k7cL-nTJoUA-4uyYCy-72XdSh-ihwGmq-2Y2a2e-bRYPdp-8UaaC-4uyYBU-67zKbR-fvctUK-hnadVx-nzmou3-fyCRbq-74J1y3-mToFgi-cCD4rU-bD4WAb-bLkb9R-bRYSBM-bD54Ed-bN5Pt-cCEWaA-8gtqKj-9B9dZv/">Anita363</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc/4.0/">CC BY-NC</a></span></figcaption></figure><p>Humans have <a href="http://news.discovery.com/human/evolution/why-cant-humans-regenerate-body-parts-130823.htm">some regenerative abilities</a> but compared to creatures like the salamander, which has an amazing ability to regenerate after injury, we’re pretty limited. Not only are salamanders the only adult vertebrates able to regrow full limbs, they’re able to regenerate an impressive repertoire of complex structures including parts of their hearts, eyes, spinal cord and tails.</p>
<p>In recent years, researchers have been <a href="http://www.livescience.com/34513-how-salamanders-regenerate-lost-limbs.html">studying salamander regeneration</a> in the hope that the knowledge gathered would contribute to understanding how can they regenerate, and how to promote human regeneration.</p>
<p>Although we do not yet understand the exact mechanisms by which salamanders are able to regrow their limbs, we do know that in this animal regeneration takes place by the reprogramming of adult cells. This means that for regeneration to take place, adult cells – such as muscle cells – that form the limb have to lose their muscle identity and proliferate to give rise to new cells that will contribute to form the new structure. </p>
<p>This process is rarely found in mammalian cells and this has been suggested as the basis for their poor regenerative abilities. But clearly, unravelling the mechanisms underlying this reprogramming is central to understanding why certain vertebrates can regenerate their limbs while others can’t, and how to repeat this process in humans. If we were able to crack this puzzle, it could lead to strategies to enhance the reprogramming of cells from patients, and to better understand their disease and design appropriate cures.</p>
<p>We recently found a critical component of the reprogramming mechanism. In our study, published in Stem Cell Reports, we demonstrated that the sustained activation of a molecular pathway (a group of molecules in a cell that work together to control a particular function or functions) – called the ERK pathway – plays a key role during the natural reprogramming of salamander muscle cells. Only when the ERK pathway is constantly switched “on” are the cells able to re-enter the cell cycle, which is key to their regenerative potential. </p>
<p>We also compared salamander and mammalian muscle cells. In contrast to salamander cells, we found that mammalian cells can only activate the ERK pathway transiently, and fail to keep the pathway switched “on”. Critically, we found that if we forced these mammalian cells to keep the ERK pathway activated (by giving them a piece of DNA that allows them to produce a protein that activates the pathway), the cells could produce the proteins involved in cell cycle re-entry. This suggests that the manipulation of the pathway could contribute to therapies to enhance the regenerative potential in humans.</p>
<p>Our results also suggest that the ability to trigger sustained ERK activation may underlie the generation of cells with regenerative potential in different species. This also helps us understand the vital and important question of why only a few organisms can regenerate body structures, and limbs in the case of salamanders, whereas most cannot. All this bring us a step closer to being able to regenerate complex structures in humans. </p><img src="https://counter.theconversation.com/content/28225/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Max Yun sits within the Institute of Structural and Molecular Biology at UCL</span></em></p>Humans have some regenerative abilities but compared to creatures like the salamander, which has an amazing ability to regenerate after injury, we’re pretty limited. Not only are salamanders the only adult…Max Yun, Research Fellow, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/160932013-07-17T05:39:24Z2013-07-17T05:39:24ZHippos and bumblebee bats can teach us about cancer<figure><img src="https://images.theconversation.com/files/27482/original/m4kcj3d7-1373893010.jpg?ixlib=rb-1.1.0&rect=3%2C0%2C2498%2C1565&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">How does a hippo know it should be big?</span> <span class="attribution"><span class="source">PA/David Cheskin</span></span></figcaption></figure><p>Mammals display an incredible diversity in size. The largest mammal, the blue whale, can grow up to 30m long and weigh up to 200 tonnes. Now compare that to the Bumblebee bat, which is 3cm long and weighs in at only 2g. </p>
<p>To put these figures into perspective: 30m is as tall as the ten-story <a href="http://www.youtube.com/watch?v=2NXK8pkL8ec">Instacon building</a> that was recently built in India; 200 tonnes is the weight of a 747 airliner; and a banknote can weigh 1g.</p>
<h2>Size matters</h2>
<p>So how does a blue whale “know” to be that big? And why don’t we have <a href="http://www.youtube.com/watch?v=G9hJK4fCq4U">tiny hippos</a> or enormous mice? And what can size control in mammals tell us about cancer and regenerative medicine?</p>
<p>The organs of animals are proportional to body size. The blue whale’s heart weighs 600kg and is the size of a small car while our lungs fit perfectly within our chest. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/27556/original/d8vk34yr-1373992947.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/27556/original/d8vk34yr-1373992947.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=393&fit=crop&dpr=1 600w, https://images.theconversation.com/files/27556/original/d8vk34yr-1373992947.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=393&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/27556/original/d8vk34yr-1373992947.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=393&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/27556/original/d8vk34yr-1373992947.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=494&fit=crop&dpr=1 754w, https://images.theconversation.com/files/27556/original/d8vk34yr-1373992947.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=494&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/27556/original/d8vk34yr-1373992947.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=494&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">He’s having a whale of a time.</span>
<span class="attribution"><span class="source">PA/David Parry</span></span>
</figcaption>
</figure>
<p>But if you compare cells taken from a whale and a miniature bat, they are the same size. We know then that the size of an animal is controlled by the number of cells in each tissue. And it’s the balance between cell growth and cell death that controls when an organ stops growing. </p>
<p>As cancer is caused by uncontrolled growth of cells, a better understanding of how cells decide to grow or die has important ramifications for health and disease.</p>
<h2>The Hippo pathway</h2>
<p>It has only been in recent years that the molecular and cellular pathways that control organ size have been studied. It has been known for many years that when cells grow in a test tube, they stop dividing when they come in contact with other cells. </p>
<p>This “cell-contact” mechanism mediates growth and is defective in cancer cells, which continue to grow even when they are extremely crowded. </p>
<p>In many animals, including flies, mice and humans, tissue overgrowth is triggered by faulty signalling systems. One of these signalling systems was recently identified and called the <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124840/">Hippo pathway</a>, a tongue-in-cheek nod to the size of hippos. </p>
<p>Mutations in this pathway lead to a massive increase in organ size because of uncontrolled growth of cells. There is now an explosion of research into how the Hippo pathway is regulated in normal tissue, as well as during cancer. But our new study, published last week in <a href="http://bit.ly/18lFXD4">Developmental Cell</a>, identifies a novel mechanism that controls this pathway.</p>
<p>The Hippo pathway is activated by contact with cells. When that happens, chemical signals within the cell cause a protein called Yap - or Yes-associated protein - to be switched off. The Yap protein causes cells to recognise that it’s time to stop dividing but if the signalling system is faulty, Yap isn’t inactivated and tissue and organs continue to grow.</p>
<p>We’ve seen it in flies or mice that lack the ability to inactivate Yap - cells continue to grow, leading to larger organs and ultimately cancer.</p>
<h2>Using proteins to send messages</h2>
<p>Signalling pathways use several proteins in the body to pass along a message from outside the cell into the nucleus of the cell, which changes the way the cell behaves. How proteins pass along this signal varies depending on what the ultimate message is. </p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/27559/original/xx395y47-1373999915.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/27559/original/xx395y47-1373999915.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=821&fit=crop&dpr=1 600w, https://images.theconversation.com/files/27559/original/xx395y47-1373999915.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=821&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/27559/original/xx395y47-1373999915.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=821&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/27559/original/xx395y47-1373999915.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1032&fit=crop&dpr=1 754w, https://images.theconversation.com/files/27559/original/xx395y47-1373999915.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1032&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/27559/original/xx395y47-1373999915.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1032&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A Yes-Association protein gets the chemical treatment.</span>
<span class="attribution"><span class="source">Flickr/Nikki Pugh</span></span>
</figcaption>
</figure>
<p>A common way the body creates different messages is by using chemicals to modify proteins, which then affects their ability to interact with the next link in the chain. </p>
<p>For the Hippo pathway and inhibiting cell growth, it’s the addition of a phosphate group of chemicals on the Yap protein that inactivates it. Our results also identify that an additional chemical modification - methylation - controls how Yap works - and ultimately the way the Hippo pathway works.</p>
<p>When we began this project, our focus wasn’t turned towards this signalling system but on the role of an enzyme called Set7. But differences we saw in the structure of the gut in the mice we studied and the publication of the another study into the characteristics of mice that had a mutation in their Hippo pathway, led to a series of experiments also linking Set7 and a role in inhibiting Yap - and therefore cell growth.</p>
<h2>Cancer drugs</h2>
<p>The ramifications of our findings are diverse. Our findings suggest that drugs that can block Set7’s function could result in more cell growth, which could improve regenerative processes such as tissue repair in people who have suffered damage. </p>
<p>But activation of Set7 could potentially increase the inhibition of Yap and thereby slow cell growth, creating a potential new cancer therapy. </p>
<p>We have yet to work out whether manipulation of Set7 during foetal development would have any drastic effect on tissue size - allowing us to create giant bumblebee bats for example. Or whether Set7 works differently in small or large animals. And for now, we still have very little understanding of all of the intricacies of this exciting Hippo pathway. </p>
<p>So unfortunately it will still be a while until <a href="http://www.youtube.com/watch?v=G9hJK4fCq4U">house hippos</a> are a reality.</p><img src="https://counter.theconversation.com/content/16093/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Colby Zaph receives funding from the Canadian Institutes of Health Research.</span></em></p>Mammals display an incredible diversity in size. The largest mammal, the blue whale, can grow up to 30m long and weigh up to 200 tonnes. Now compare that to the Bumblebee bat, which is 3cm long and weighs…Colby Zaph, Assistant professor of Pathology and Laboratory Medicine , University of British ColumbiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/35522011-10-02T19:19:26Z2011-10-02T19:19:26ZGus Nossal: It’s Australian Jacques Miller’s turn for a Nobel Prize<figure><img src="https://images.theconversation.com/files/3978/original/Miller_at_microscope.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Jacques Miller discovered the function of the thymus gland, which changed immunology forever.</span> </figcaption></figure><p>Every year at the beginning of October, a frisson runs through the global medical research community. Who will win the greatest lottery of them all, the <a href="http://www.nobelprize.org/">Nobel Prize</a> for Medicine? </p>
<p>In a cynical and sceptical world, here is one status symbol that has not lost its magic.</p>
<p>This year, the matter has an extra piquancy for Australia. The <a href="http://science.thomsonreuters.com/nobel/2011predictions/#medicine">media has speculated</a> that it might at last be the turn of <a href="http://www.wehi.edu.au/">Walter and Eliza Hall Institute’s (WEHI)</a> Professor <a href="http://www.wehi.edu.au/about_us/leadership/wehi_laureates/">Jacques Miller</a>, whom I’ve <a href="http://www.theage.com.au/victoria/veterans-celebrate-a-golden-era-at-walter-and-eliza-hall-20110602-1fiwm.html">previously described</a> as the single living individual most deserving of a Nobel Prize, to receive it.</p>
<p>A large claim? Let’s examine the facts.</p>
<h2>The unknown organ</h2>
<p>Before Miller’s work, the <a href="http://en.wikipedia.org/wiki/Thymus">thymus gland</a> represented a deep mystery.</p>
<p>It’s a large gland situated behind the breastbone, sitting in front of the heart. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/3971/original/Gray_s_Anatomy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/3971/original/Gray_s_Anatomy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=443&fit=crop&dpr=1 600w, https://images.theconversation.com/files/3971/original/Gray_s_Anatomy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=443&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/3971/original/Gray_s_Anatomy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=443&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/3971/original/Gray_s_Anatomy.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=556&fit=crop&dpr=1 754w, https://images.theconversation.com/files/3971/original/Gray_s_Anatomy.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=556&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/3971/original/Gray_s_Anatomy.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=556&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption"></span>
<span class="attribution"><span class="source">Gray's Anatomy, 1918.</span></span>
</figcaption>
</figure>
<p>When examined under the microscope, the thymus gland contains billions of small round cells that look just like white blood cells known as small <a href="http://thyroid.about.com/library/immune/blimm06.htm">lymphocytes</a>. </p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/3973/original/Lymphocyte_National_Cancer_Institute.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/3973/original/Lymphocyte_National_Cancer_Institute.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=551&fit=crop&dpr=1 600w, https://images.theconversation.com/files/3973/original/Lymphocyte_National_Cancer_Institute.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=551&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/3973/original/Lymphocyte_National_Cancer_Institute.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=551&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/3973/original/Lymphocyte_National_Cancer_Institute.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=693&fit=crop&dpr=1 754w, https://images.theconversation.com/files/3973/original/Lymphocyte_National_Cancer_Institute.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=693&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/3973/original/Lymphocyte_National_Cancer_Institute.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=693&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Electron microscopic image of a single human lymphocyte.</span>
<span class="attribution"><span class="source">National Cancer Institute.</span></span>
</figcaption>
</figure>
<p>These lymphocytes also occur in lymph nodes, the spleen, tonsils and adenoids and numerous other collections of lymphatic tissue. </p>
<h2>Defence system</h2>
<p>Past research had proven that lymphocytes from such lymphoid tissues were the main warriors of nature’s defence system, the immune system. </p>
<p>When properly stimulated with vaccine molecules (or antigens), they multiply, begin to form antibody molecules, or mount a direct attack on invading micro-organisms. This process is known as cell-mediated immunity. </p>
<h2>Unknown function</h2>
<p>Cells derived from the thymus had no such power to mount an attack, or were weak, at best. </p>
<p>And when the thymus was surgically removed in an adult mouse, its immune response wasn’t impaired. It was clear there was something very different about thymus lymphocytes compared with other lymphocytes.</p>
<p>Without any meaningful function for the thymus, scientists struggled to understand it. One idea was that it was a graveyard for dying lymphocytes. </p>
<p>Another was that it was some kind of evolutionary relic, like the appendix, without any present function.</p>
<p>But a line of research, which had little to do with cellular immunology, revealed a surprising fact about the thymus: when it was removed from mice, they didn’t develop certain forms of leukaemia. </p>
<p>Somehow the thymus was essential in the genesis of such leukaemias. </p>
<h2>Initial investigations</h2>
<p>Miller was interested in studying leukaemias that might have been associated with a virus. Thymus removal (thymectomy) in adult life did not prevent such leukaemias. </p>
<p>Noting that some of these leukaemias appeared very early in life, Miller taught himself to do thymectomies at younger and younger ages. </p>
<p>Finally, he managed to remove the thymus within just a few hours of the mice being born. </p>
<p>Bearing in mind that these little animals weighed less than a gram, this was an extraordinary feat. So was keeping the operated sucklings alive and stopping the mothers from eating them! </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/3975/original/Jacques_Miller_old.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/3975/original/Jacques_Miller_old.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=410&fit=crop&dpr=1 600w, https://images.theconversation.com/files/3975/original/Jacques_Miller_old.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=410&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/3975/original/Jacques_Miller_old.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=410&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/3975/original/Jacques_Miller_old.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=515&fit=crop&dpr=1 754w, https://images.theconversation.com/files/3975/original/Jacques_Miller_old.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=515&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/3975/original/Jacques_Miller_old.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=515&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Jacques Miller, a “peerless experimentalist”, in his early career.</span>
<span class="attribution"><span class="source">WEHI</span></span>
</figcaption>
</figure>
<p>When the neonatally thymectomized mice grew up, several striking abnormalities were noted. </p>
<p>First, they were very prone to all kinds of infections, and actually failed to thrive in comparison to mice with thymus glands. </p>
<p>But when the mice were raised in a germ-free environment, their growth pattern was normal. </p>
<p>So their runt status was the result of their immune system’s failure to protect them from infections. </p>
<p>Miller then challenged their immune systems in various ways. He gave them standard vaccines and the responses were sub-normal. </p>
<p>He placed foreign skin grafts into their coats. These would normally be rejected within seven to 10 days, but in the neonatally-thymectomized mice, skin grafts survived and grew a luxurious growth of hair (he even grafted white skin on a black mouse). </p>
<p>Later in life, a disproportionately high percentage of the mice developed leukaemia and other cancers. This showed the thymus, in very young life, was critical to the correct development of the immune system. </p>
<p>It could be argued that the thymus was in fact the mastermind of the immune system. </p>
<p>In the crucial first days and weeks of the mouse’s life, it exported immunologically competent cells to the rest of the body. </p>
<p>As these colonised the various lymphoid tissues, living for a very long time, the thymus became less important.</p>
<h2>Help arrives</h2>
<p>In 1966, Miller was joined by a gifted veterinary science graduate who embarked on a PhD with him: <a href="http://www.wehi.edu.au/about_us/history/the_nossal_era/">Dr Graham F. Mitchell</a>. </p>
<p>Together, they demonstrated that small lymphocytes – which all look so similar under the microscope – actually fall into two broad classes. These later came to be called T and B lymphocytes. </p>
<p>T cells are derived from the thymus and B cells from the bone marrow. </p>
<p>They showed it was actually the B cells that made the precious antibody molecules that keep us immune to many diseases; whereas the T cells were responsible for cell-mediated immune responses such as skin graft rejection or delayed hypersensitivity. </p>
<p>Most surprisingly, for many antibody responses, the T cells were actually needed to help the B cells in their task of antibody production.</p>
<p>Such novel and provocative findings were not accepted instantly. </p>
<p><a href="http://www.ox.ac.uk/media/science_blog/100716.html">Sir James Gowans</a>, the doyen of British immunologists, long maintained that lymphocytes consisted of a single, uniform, homogeneous population. </p>
<p>While he recanted when the evidence became overwhelming, another senior immunologist, the Australian <a href="http://www.eoas.info/biogs/P001511b.htm">Professor Bede Morris</a> never did. His immortal comment was that the only significance of B and T cells was that they constituted the first and last letters of the word “bulls**t”. </p>
<p>Miller’s key findings were independently confirmed fairly rapidly.</p>
<h2>Impact of the discovery</h2>
<p>Miller is the last person to discover the function of a human organ — the thymus — and not a single chapter of immunology has been untouched by the discovery. </p>
<p>T cells became even more prominent when it became clear that they were the chief target of the AIDS virus. </p>
<p>Miller continued to make discoveries about the thymus and T cells for many decades, including gaining important insights into:</p>
<ul>
<li><p>how the immune system discriminates between self and non-self; </p></li>
<li><p>how it goes wrong in autoimmune diseases; and</p></li>
<li><p>how the whole orchestra of the immune system is regulated. </p></li>
</ul>
<p>All of this is covered in 400 scientific papers.</p>
<h2>Recent accolades</h2>
<p>For the 50th anniversary of the first thymus findings (September 2011) Miller was asked to provide a <a href="http://www.nature.com/nri/journal/v11/n7/abs/nri2993.html">summary of his life’s work for Nature</a>. </p>
<figure class="align-left ">
<img alt="" src="https://images.theconversation.com/files/3977/original/Jacques_Miller_older.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/3977/original/Jacques_Miller_older.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=901&fit=crop&dpr=1 600w, https://images.theconversation.com/files/3977/original/Jacques_Miller_older.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=901&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/3977/original/Jacques_Miller_older.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=901&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/3977/original/Jacques_Miller_older.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1133&fit=crop&dpr=1 754w, https://images.theconversation.com/files/3977/original/Jacques_Miller_older.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1133&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/3977/original/Jacques_Miller_older.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1133&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Jacques Miller is now a WEHI Laureate and an Emeritus Professor at The University of Melbourne.</span>
<span class="attribution"><span class="source">WEHI</span></span>
</figcaption>
</figure>
<p>And in June 2011, The Walter and Eliza Hall Institute ran a celebratory symposium in Melbourne. </p>
<p>Is it possible that the venerable ladies and gentlemen of the Medical Faculty of the Karolinska Institute in Stockholm were reading and listening?</p>
<p>Miller’s work has been honoured by the international scientific community with several prizes: the <a href="http://royalsociety.org/awards/copley-medal/">Copley Medal</a>, the Royal Society’s highest honour barring the Presidency; Germany’s top prize, the <a href="http://en.wikipedia.org/wiki/Paul_Ehrlich_and_Ludwig_Darmstaedter_Prize">Paul Ehrlich-Ludwig Darmstaedter Prize</a>; and Canada’s famous Nobel predictor, <a href="http://www.gairdner.org/">The Gairdner Foundation Annual International Award</a>. </p>
<p>Those of us who have known Jacques for a lifetime didn’t need these external signals of his worth. </p>
<p>We esteem him as a peerless experimentalist, an inspiring research mentor, an embracer of impeccably high standards of scientific rigour and integrity. In short, Miller is a paragon of the noble profession of medical research which he graces. </p>
<p>Still full of ideas and vigour at the age of 80, long may he continue his life’s lofty mission.</p><img src="https://counter.theconversation.com/content/3552/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gustav Nossal worked with Jacques Miller at the Walter & Eliza Hall Institute (WEHI).</span></em></p>Every year at the beginning of October, a frisson runs through the global medical research community. Who will win the greatest lottery of them all, the Nobel Prize for Medicine? In a cynical and sceptical…Gustav Nossal, Professor Emeritus , Walter and Eliza Hall InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/34292011-09-19T23:26:28Z2011-09-19T23:26:28ZWonder organ – how the liver finds and destroys immune cells<figure><img src="https://images.theconversation.com/files/3713/original/hettie_gm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A new study shows the liver destroys the cells responsible for rejected organ transplants.</span> </figcaption></figure><p>Most people only think about their liver when recovering from a big night of drinking when it’s busily producing enzymes to break down the alcohol. But this “factory” of the body is vital for survival and supports almost every organ. </p>
<p>If you didn’t have a liver, you wouldn’t be able to store carbohydrates and you couldn’t produce the bile that helps you digest a greasy breakfast. </p>
<p>We’ve known for around 40 years that the liver also has the ability to regulate the immune system’s response to foreign cells.</p>
<p>Now some colleagues and I at the <a href="http://www.centenary.org.au/">Centenary Institute</a> have discovered how the liver fights the immune system. We’ve identified (in mice) that the liver engulfs and destroys T cells – the body’s defence troops.</p>
<p>Our work, <a href="http://www.pnas.org/content/early/recent">published today</a> in the journal <a href="http://www.pnas.org/">Proceedings of the National Academy of Sciences</a> (PNAS), could lead to new approaches to prevent transplant rejection. It could also change the way we fight hepatitis C and other chronic liver diseases.</p>
<h2>The discovery</h2>
<p>My colleague Dr David Bowen and I first realised the liver could eliminate the T cells responsible for rejecting transplanted tissue around ten years ago. The T cells are also responsible for killing cells infected with viruses.</p>
<figure class="align-right ">
<img alt="" src="https://images.theconversation.com/files/3710/original/liver-01.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/3710/original/liver-01.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=600&fit=crop&dpr=1 600w, https://images.theconversation.com/files/3710/original/liver-01.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=600&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/3710/original/liver-01.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=600&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/3710/original/liver-01.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=754&fit=crop&dpr=1 754w, https://images.theconversation.com/files/3710/original/liver-01.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=754&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/3710/original/liver-01.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=754&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A T-cell (blue/green) being drawn into a mouse liver cell (red).</span>
</figcaption>
</figure>
<p>We found T cells rapidly disappeared when they entered the liver but were puzzled about how and why this occurred.</p>
<p>It was only in 2004, when our collaborator Dr Alessandra Warren at Concord Hospital took electron microscopy pictures showing live immune cells (T cells) inside healthy liver cells, that we came up with the idea that T cells might be “eaten” by liver cells. This was a true eureka moment.</p>
<p>When I presented this concept to Volker Benseler, a talented German post-doc at the time (now the lead author of the PNAS paper), he was sceptical and thought the idea was crazy. But he accepted the challenge and went on to discover healthy mouse liver cells eating T cells. </p>
<p>Until then, this kind of “cell cannibalism” had only been seen in tumour cells. </p>
<h2>Suffering from rejection</h2>
<p>One potential benefit of the research is a reduction in organ transplant rejections. </p>
<p>About 200 liver transplants are performed in Australia each year and up to a quarter of the cases end in rejection. </p>
<p>In transplantation, the new organ is seen by the body as a foreign object: the spleen or lymph nodes tell naïve T cells to replicate and turn into killer T cells. They are then sent off kill the “foreign” cells.</p>
<p>What we found was the liver circumvented this process: liver cells signal to naïve T cells and destroy them before they have a chance to become killer T cells.</p>
<p>If we can harness the way the liver controls T cells, then there’s a chance that transplant patients won’t need their current daily cocktail of immunosuppressive drugs.</p>
<p>While these drugs reduce the risk of organ rejection, they essentially wreck the patients’ immune systems and leave them open to serious infection from otherwise minor illness such as colds. </p>
<p>The immunosuppressive drugs also predispose the patient to long-term heart disease and cancer.</p>
<h2>Battling hepatitis </h2>
<p>Another spin-off of this latest work could be finding a way to tone down the liver’s destruction of T cells and increase its defence against infections, such as hepatitis. </p>
<p>In Australia, 217,000 people are living with chronic hepatitis C and it’s estimated that 170 million people worldwide are infected with the disease, for which there is no vaccine.</p>
<p>With further bimolecular research, we could develop medications that exploit the signal pathways between the liver and the T cells. To defend against hepatitis C, we need to develop drugs that prevent T cells from being digested by the liver to encourage the generation of killer cells that will ultimately eliminate the virus.</p>
<p>For transplants, we need to develop drugs that do the opposite and promote T cell degradation in the liver.</p>
<p>It could be another ten years or more before any drug derived from this work enters clinical trials. But in the meantime, we’ve got some exciting work ahead of us.</p><img src="https://counter.theconversation.com/content/3429/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Patrick Bertolino receives funding from NHMRC. He works at the Centenary Institute.</span></em></p>Most people only think about their liver when recovering from a big night of drinking when it’s busily producing enzymes to break down the alcohol. But this “factory” of the body is vital for survival…Patrick Bertolino, Senior Research Fellow, Head of the Liver Immunology Group, Centenary InstituteLicensed as Creative Commons – attribution, no derivatives.