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MDCK (Madin-Darby canine kidney) cell lines derived of an english cocker spaniel are used in cancer research to determine the molecular basis of malignancies in dogs. Credit: Susanna Berger/Vetmeduni Vienna Dogs get cancer, just like humans. Scientists at the University of Veterinary Medicine, Vienna are now exploring the molecular basis of cancer progression in canine cell lines. Modern cancer therapy has been revolutionized with the introduction of new drugs, so-called 'targeted drugs', but the basis for the application of these new agents in cancer therapy is a deep understanding of the molecular mechanisms of the disease, even with pets. Now a research team led by Sabine Macho-Maschler has investigated the activation of genetic regulatory mechanisms in canine cells and found both matches as well as differences compared to man. Almost every second dog above the age of ten years develops cancer. Modern tumor therapy combines surgery, radiation therapy and novel drug treatment options. While surgery and radiotherapy ensure adequate treatment for all animals at the University of Veterinary Medicine, Vienna, there is a growing gap in the treatment with modern therapeutics. The reason for this is that modern targeted agents are based on specific molecular genetics findings, which are not easy to transfer to dogs from humans or the preferred animal model in cancer research, the mouse. So to make modern cancer drugs also accessible to our four-legged friends requires comparative research into the molecular basis of cancer in dogs. Molecular causes constitute an important basis for modern treatment concepts Our understanding of the molecular and cellular causes that are responsible for the development of cancer has grown strongly in recent years. This knowledge aids us in combating cancer cells with a growing number of new drugs. However, since cancer may manifest itself differently in each patient, an extensive molecular study of the existing mutations in cancer cells is an important prerequisite for successful therapy. This is because the targeted agents can only actually help when the cancer cells possess the corresponding molecular structures against which the drug is designed to act. The success of treatment with targeted drugs requires a molecular diagnosis, as basis for the so-called 'personalized medicine' in cancer research. Investigation into the molecular mechanisms of metastasis in canine cells A research team at the Unit of Molecular Genetics have investigated an important process in the molecular genetics of cancer development in canine cell lines. These cell lines have long been used by researchers to analyze pathological processes and now were analyzed for changes in the expression of several RNA-species using next generation sequencing. "Cancer researchers have been working for many years on the transition of epithelial tumor cells into the more aggressive mesenchymal state. Important gene switches could be identified in this process with potential for use as therapeutic targets: these gene products could be targeted with novel therapeutics", explained Macho-Maschler, who headed the now published study. Research on epithelial-mesenchymal transition (EMT) has so far mainly focused on cells of mice and humans and showed how certain signaling pathways cooperate to allow cancer cells metastasis. Metastases are formed when the originally sedentary cancer cells obtain certain properties, which allow them to migrate into another organ and to form a new tumor there. "In the majority of cases it is the metastases that cost the patient's live, as the original tumor can often be well controlled by radiation and surgery," emphasized Mathias Müller, head of the Institute for Animal Breeding and Genetics. "We are interested in what is going on at the molecular level during metastasis, as it is likely that we can use this knowledge for the successful treatment of metastases." The basis for further research has been laid The molecular analysis of EMT is considered by researchers as a model for the acquisition of the ability to metastasize. The TGF-beta pathway has for a long time been recognized as a central switch in this process. Macho-Maschler expressed her satisfaction with the many similarities seen in the comparative analysis of results for canine, human and mouse cells. "TGF-beta, for example, also plays an important role in dogs, but there are also interesting variations," reports Macho-Maschler. Her recent BMC Genomics publication is filled with long lists of RNAs that are regulated during EMT. These findings should serve as a basis for further analysis. Macho-Maschler is skeptical as to whether their research can improve the treatment of dogs with cancer in the near future. "Our newly published results are like a catalogue, perhaps an important requirement for new approaches and ideas. Ultimately, we do not even know whether many of the new drugs actually act in canine cells. There are, for example, targeted drugs which act only in humans but not in mice" says Macho-Maschler to dampen unrealistic expectations. In humans, a much more comprehensive catalogue was completed this year; "The Cancer Genome Atlas" makes available to researchers the essential information contained within 11,000 genetically analyzed patient samples (cancergenome.nih.gov). It is an important resource, which enables researchers quickly and reliably to check the frequency of certain genetic changes in a cancer. The catalogue published by Macho-Maschler is naturally not comparable with the TCGA, but it is a first important step in the same direction for canine cancer. Explore further: First cancer immunotherapy for dogs developed More information: Priyank Shukla et al. High-throughput mRNA and miRNA profiling of epithelial-mesenchymal transition in MDCK cells, BMC Genomics (2015). DOI: 10.1186/s12864-015-2036-9

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A group of 48 biologists and physical scientists from 50 institutions is aiming to change that. In the October 30 issue of the journal Science, they called for an ambitious research effort to understand and harness microbiomes. Such research could lead to advances in fields as diverse as medicine, child development, agricultural productivity, and climate modeling. Now, in a far-ranging roundtable discussion, three of the paper's co-authors explain to The Kavli Foundation why this is the time to launch a major national effort—the Unified Microbiome Initiative—to study the planet's least understood ecosystems. "In the past, we did not fully understand the complexity and richness of microbiomes, and we were limited because we could not grow the majority of bacteria in a lab, and so they were hard to study," explains Janet Jansson. Jansson is Chief Scientist of Biology in the Earth and Biological Sciences Directorate at Pacific Northwest National Laboratory (PNNL) and sector lead for PNNL research in the Department of Energy's Biological Systems Science Division. Over the past 15 years, however, the cost of genome sequencing has fallen by a factor of 1 million. This made it possible for the first time to survey the richness of microbial communities. The research has led to the discovery of hundreds of new and unexpected bacterial phyla, which are large groupings of related lifeforms. New genomic tools have vastly expanded our understanding of the role microbiomes play in our lives, Rob Knight explains. He is a founder of the American Gut Project and holds joint appointments at the University of California, San Diego, School of Medicine and Department of Computer Science and Engineering. "Remember, 10 years ago, microbes hadn't been linked to any of the things we now know they're involved in, such as obesity, allergies, depression and brain development. While the links between the microbiome and metabolism have certainly been very surprising, what surprised me the most has been the links between the microbiome and behavior. This was not even on the radar 10 years ago," Knight says. The Unified Microbiome Initiative calls for developing a new generation of scientific instruments that would let researchers study how microorganisms within a community interact with one another and their environment. This knowledge would make it possible to manipulate microbiomes to improve healthcare, agriculture and the environment. The impact of microbiome research on human health alone could be profound. Over the past 10 years, researchers have discovered that the composition of the gut microbiome - which contains 10 times more cells and 100 times more genetic information than the human body - can determine how medicines are metabolized. And physicians have demonstrated that transplanting healthy microbiomes into patients afflicted with colitis, an inflammation of the lining of the colon, caused by Clostridium difficile is three to four times more effective than antibiotics. "This is actually the first proof of principle that we can manipulate microbiomes in a very deliberate way to treat a serious human disease," says Jeff Miller, lead author of the Science paper. Miller is director of the California NanoSystems Institute, holds the Fred Kavli Chair in NanoSystems Sciences, and is a professor of Microbiology, Immunology & Molecular Genetics at University of California, Los Angeles. Microbiomes also play an important role in global ecosystems. Jansson, for example, studies how microbiomes behave as Arctic permafrost thaws. She hopes to learn how this will affect the metabolism of microbiomes that cycle carbon so scientists can model the impact on climate change. Microbiomes also play an important role in agriculture, where they provide plants with essential nutrients and even enzymes. However, the ability to engineer microbiomes also raises some flags. "Whenever we manipulate something in an animal or a human being, we need to consider the ethical issues. But the idea of potentially engineering Earth's microbial ecosystems raises very legitimate questions," Miller says. Explore further: Nanoscience provides insights into the world's smallest ecosystems More information: Read the full conversation with Janet Jansson, Rob Knight and Jeff Miller at: www.kavlifoundation.org/science-spotlights/why-its-time-map-microbiome

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In a landmark discovery, researchers at Tel Aviv University have unraveled the metastatic mechanism of melanoma, the most aggressive of all skin cancers. According to a paper published today in the journal Nature Cell Biology, the scientists discovered that before spreading to other organs, a melanoma tumor sends out tiny vesicles containing molecules of microRNA. These induce morphological changes in the dermis in preparation for receiving and transporting the cancer cells. The researchers also found chemical substances that can stop the process and are therefore promising drug candidates. "The threat of melanoma is not in the initial tumor that appears on the skin, but rather in its metastasis—in the tumor cells sent off to colonize in vital organs like the brain, lungs, liver and bones," said research leader Carmit Levy of the Department of Human Molecular Genetics and Biochemistry at TAU's Sackler School of Medicine. "We have discovered how the cancer spreads to distant organs and found ways to stop the process before the metastatic stage." The TAU group worked in close collaboration with Jörg D. Hoheisel and Laureen Sander at the German Cancer Research Center (DKFZ) in Heidelberg, Shoshi Greenberger at the Sheba Medical Center at Tel HaShomer, Israel and Ronen Brenner at the Wolfson Medical Center in Holon, Israel. Lab research was led by Shani Dror of Dr. Levy's research group. Melanoma, the most aggressive and lethal type of skin cancer, causes the death of one person every 52 minutes according to data from the Skin Cancer Foundation, and the number of diagnosed cases has been on the rise for the past three decades. Despite a range of therapies developed over the years, there is still no full remedy for this life-threatening disease. The new study proposes novel and effective methods for diagnosing and preventing this most deadly of skin cancers. The researchers began by examining pathology samples taken from melanoma patients. "We looked at samples of early melanoma, before the invasive stage," Levy said. "To our surprise we found changes in the morphology of the dermis—the inner layer of the skin—that had never before been reported. Our next task was to find out what these changes were, and how they related to melanoma." In the ensuing study, the group was able to discover and block a central mechanism in the metastasis of melanoma. According to Levy, scientists have known for years that melanoma forms in the outer layer of the skin, the epidermis. At this early stage, the cancer is unable to send off colonizing cancer cells because it has no access to blood vessels—the highways that carry the cells to other parts of the body. With no blood vessels present in the epidermis, the tumor first needs to contact the abundant blood vessels running through the dermis. But how was the connection made? "We found that even before the cancer itself invades the dermis, it sends out tiny vesicles containing molecules of microRNA," Dr. Levy said. "These induce the morphological changes in the dermis in preparation for receiving and transporting the cancer cells. It then became clear to us that by blocking the vesicles, we might be able to stop the disease altogether." Having discovered the mechanism, the researchers proceeded to look for substances that could intervene and block the process in its earliest stages. They found two such chemicals: one (SB202190) inhibits the delivery of the vesicles from the melanoma tumor to the dermis; and the other (U0126) prevents the morphological changes in the dermis even after the arrival of the vesicles. Both substances were tested successfully in the lab, and may serve as promising candidates for future drugs. In addition, the changes in the dermis, as well as the vesicles themselves, can be used as powerful indicators for early diagnosis of melanoma. "Our study is an important step on the road to a full remedy for the deadliest skin cancer," said Levy. "We hope that our findings will help turn melanoma into a nonthreatening, easily curable disease."

Alan Brown is a writer and blogger for the Kavli Foundation. Read more perspective pieces on the Kavli Expert Voices landing page. Brown contributed this article to Live Science's Expert Voices: Op-Ed & Insights. Microbes could soon be at the top of the world's big-science list. Late last year, a consortium of scientists from 50 U.S. institutions proposed the "Unified Microbiome Initiative," a national effort to advance our understanding of microbiomes, communities of single-celled organisms such as bacteria, viruses and fungi. With a unified focus, researchers hope to learn how microbiomes could not only cure infectious diseases and reduce antibiotic drug resistance, but also reclaim exhausted farmland, cut fertilizer and pesticide use, and produce new fuels and carbon-based chemicals. Reaching those ambitious goals will require an equally ambitious effort to develop new tools and collaborations, building on breakthroughs in the analysis of microbial DNA, proteins and metabolites. Such analyses show that microbial communities can be incredibly diverse , including hundreds of thousands of different microbial species, all interacting with one another. In the human gut, those microbes aid digestion, but they may also impact obesity, allergies and even brain development. Beyond our bodies, microbes created the Earth's oxygen-rich atmosphere, and enable plant and ocean life to thrive. While today's tools can tell us a great deal about the molecules in microbial communities, they cannot explain the function of these molecules and how they enable microorganisms to work together. Only with that level of understanding, will scientists be able to harness microbiomes to improve human health and the environment. Recently, The Kavli Foundation hosted a Google+ Hangout about the potential of nature's microbiomes and how we can tap into it. The participants included: Janet Jansson is chief scientist of biology in the Earth and Biological Sciences Directorate at Pacific Northwest National Laboratory (PNNL) and sector lead for PNNL research in the Department of Energy's Biological Systems Science Division. She coordinates two of PNNL’s biology programs: the Microbiomes in Transition (MinT) initiative to study how climate and environmental changes impact natural and human microbiomes and the DOE Foundational Scientific Focus Area, Principles of Microbial Community Design. Rob Knight is the founder of the American Gut Project, an open-access project to survey the digestive system’s microbiome and its effect human health and development. He holds appointments at the University of California, San Diego School of Medicine and Department of Computer Science and Engineering, where he develops bioinformatics systems to classify and interpret large sets of biological data. Jeff F. Miller is director of the California NanoSystems Institute, a multidisciplinary research organization, and the corresponding author of the consortium’s Science paper. Based at University of California, Los Angeles, Miller holds the Fred Kavli Chair in NanoSystems Sciences and is a professor of Microbiology, Immunology & Molecular Genetics. Below is a modified transcript of the discussion. Edits and changes have been made by the participants to clarify spoken comments recorded during the live webcast. The Kavli Foundation: So, let's start with a question. There's been a Cambrian Explosion in microbiome research. Ten years ago, microbiomes were hardly on the map. Last year, 25,000 papers contained the term. Why is this happening now? Is it just because we can read microbial DNA, or are other technologies making this possible? Jeff Miller: There are a lot of factors that came together to cause this explosion of interest. One, certainly, is the ability to rapidly sequence DNA. And over the past 10 years or so, we've seen a progression of technologies that allow us to characterize microbial communities with increasing resolution and sophistication. But we've also encountered many bottlenecks along the way. And interpreting this massive amount of sequenced data is one of those bottlenecks. Rob Knight: I agree. I think it's really the combination of the DNA sequencing tools getting much cheaper, and the computational tools, including the toolkits that we developed, that make the information much more accessible to a broad community of users. I think what we will see in the future are tools that will go beyond taking inventories of species or inventories of genes and instead provide much more insight about how these species and genes function. But that is going to require a whole lot of additional development of both the software and the knowledge base to use that software. TKF: Janet, do you have any additional thoughts on that? Janet Jansson: Yes. With DNA sequencing we get information about the composition of microbiomes, but it's also interesting to know what those microbes are doing. For example, if we could understand their protein or metabolite composition, we could get a better understanding of what they're doing in different kinds of habitats and inside our bodies. There are a lot of developments in these areas, but those tools are still lagging behind the sequencing technologies. TKF: So, do we need a major program, a Unified Microbiome Initiative, to develop these capabilities? Couldn't we build on existing technologies or do we need to invent radically new types of science? Miller: The likely answer is, "both." There's certainly a lot of room for incremental advances leading to better sequencing technology and the like. But we also need some quantum leaps at the same time. The field has progressed rapidly. But we've reached a plateau that has to do with the limitations of the current technologies. We need to be able to see microbial communities where they live, in real time. We want to know what are they doing. What genes are they expressing? What proteins are they making? What metabolites are they synthesizing? How are they responding to each other and their environments? Then we need to be able to take all this data and interpret it in a way that allows us to ask questions and formulate new hypotheses that we can test and falsify or prove correct. These are really tall orders. They're going to require not only new technologies, but also the input of collaborators in engineering, physics, and chemistry, as well as the life sciences, environmental sciences, computer sciences, and more. TKF: I'm curious about the computer science side of it. Rob, you have a joint appointment UC San Diego's medical school and computer science department. Is it such a tall order? I mean, we have big data. Are we going to need something more? Knight: Well, the issue is that big data and magic are not quite the same thing. There's a lot of advances that need to happen on the algorithm side. In general, machine learning and generic algorithms will give you a good, but not ideal, answer to a particular scientific question. And the more information you can put in at the beginning to tailor those algorithms to your specific problem, the better you'll do. The other thing is that although we're producing a tremendous amount of data, we're still limited by the amount of data—it’s still not enough—and by our ability to interpret it. The problem a lot of people are facing right now is that they have collected so much microbial community information. They have over a thousand species that they don't understand. They are listing a million genes they don't understand. Then they are going onto measuring other types of molecules using metatranscriptomics or metaproteomics or metabolomics where, again, they create very large inventories that they also don't understand. But even with all that data, we're still limited by the number of samples, and by our ability to annotate and understand those entities. There's a huge role for both existing algorithms that can be applied more effectively as we get more data, and for fundamentally new algorithms as well as new ways of computing that radically change how we think about computation itself. TKF: Part of the challenge is that we need a better way to get closer to the inhabitants of metaphorical city I mentioned earlier. It is as if we are looking at that city from space and trying to figure out people's roles when we cannot even see these individuals, isn't it? Knight: It's a little worse than that. You're flying out there in your UFO, and you just take a big chunk of that city, grind it up, look at all the DNA and chemicals, and try to make sense of it. That can be an effective or ineffective way to understand the city. You will get an understanding of some of the chemical processes that are going on, and some of the genes that are expressed. But you're not going to learn a lot about the sociology or how those organisms communicate. Jansson: Yes, and another way to tackle that problem is to use simpler model communities. That way, if we don't have the instruments and data tools to deal with these highly complex communities, at least have a model community that will let us study specific interactions. TKF: In other words, it's easier to study something much simpler? Jansson: Yes, at least for now. Full communities are some of the most diverse types of habitats for microorganisms on earth. We go so much data, that we're not limited by the amount of data we produce, but by our ability to process the data. Even with supercomputers, it can take weeks, if not months, to just run all of that data through our computers. Knight: With all due respect, I think we're still data limited because we don't have enough samples. So, it's as if we had, say, five photos, and we're taking them at higher and higher resolution. That generates a lot of data, but not enough to create a movie. What we really need is, say, 100,000 frames. And no matter how much more information we get out of the smaller number of frames you have, we'll never be able to put that movie together. So, that's a lot of what we're facing. Right now, it's so expensive to process each sample, it's really difficult to get enough samples. This is really why we need to be able to read out microbes much, much faster, much, much cheaper. And we also need to use higher and higher resolution techniques, to get that full movie of how the interactions are taking place. Jansson: I agree we need more samples. But even then, it's very difficult to process the information from one sample. Miller: Right. In fact, we know the functions of only about half of the genes that we detect in these communities. And of the half we think we know, the amount of mis-annotation and improper context annotation, are also significant. So we're trying to put a puzzle together with only some of the pieces. And if you look at small molecules, this situation is even worse. About two percent of the metabolites that are found in the typical microbial community map to known structures. And only a fraction of those two percent are on known biochemical pathways. So we need more information. TKF: Those metabolites are involved in bacterial digestion. Are they how bacteria communicate with one another? Miller: Yes, that how they communicate, and how they acquire energy. They are the waste products they release, and the small molecules they use to compete with other microbes and interact with their environments. And many other things that have yet to be discovered. These small molecules are the language of microbial communities. TKF: Getting a handle on all this sounds like an imposing research project. But suppose you had these tools today. What is it that you'd like to study? Jeff, you study the evolution of bacteria that cause disease. What would you do with those tools? Miller: Boy, great question. I think one area that is prime for progress -- and some progress has been made already -- is the idea of taking a community that may be somewhat robust but not really optimal for its environment or host and engineering it so that it has more beneficial properties and fewer non-beneficial properties. Doing that really requires an understanding of the ecological principals that govern the community's composition, robustness, response to changes, etcetera. So, being able to reprogram microbial communities is really one of our ultimate goals. There are various steps along that pathway that one can imagine. But we're just at the very early stages of being able to do that. So if I were to choose one thing to study, it would be to understand how microbial communities are constructed well enough to enable predictive reliable, reengineering of those communities in order to optimize their functions. TKF: Very interesting. Janet, I know you collaborate on human microbiome work. But you've also developed a reputation for investigating how environmental changes affect microbiomes in the Alaskan permafrost and on the Gulf of Mexico. What types of things have you learned and what would new tools tell you that you don't already know? Jansson: For environmental studies, we want to understand how events, such as the Deepwater Horizon oil spill on the Gulf or the thawing of permafrost due to global warming in Alaska, is impacting microbes and the processes that they carry out in those systems. With the Gulf oil spill, we had organisms that were enriched during the spill, and that were able to degrade oil. So that was interesting, from that perspective. In the permafrost, we have a huge reserve of carbon that is currently trapped in that environment. So what happens to that carbon as the permafrost thaws and the microorganisms start to become active and degrade the carbon? Are they going to release a lot more carbon dioxide to the atmosphere and make the global warming process worse? At a very fundamental level, we need to understand what those microorganisms are doing. TKF: Very good. I'd like to move to some listener questions. You know, microbiomes are suddenly in the news, and several listeners want to know about products that promise to improve our health and cure certain conditions by altering our microbiomes. Rob, you've been studying the American gut for a while now. Do we know enough about microbiomes for anybody to make that kind of a claim? Knight: Yes, but so far, that's limited to just a very small number of people. For example, there was a really nice paper in Cell by Eran Segal and Eran Elinav of Israel's Weizmann Institute of Science. It showed that based on your microbiome, you can predict what foods will have good or bad impacts on your blood sugar. The drawback, so far, is that they can only do that in the Israeli population, where the food item inventory is somewhat different from what you would see in the United States, for example. But that technology is on the horizon and improving very rapidly. As far as probiotics go, there's not a lot of evidence that probiotics improve general health in humans, though there is some intriguing data in mice. On the other hand, there's a fair number of probiotics that have been clinically studied in well-conducted randomized controlled trials. For a number of conditions, like, irritable bowel syndrome, post-antibiotic diarrhea, and so forth, there are particular probiotics on the market that have been clinically validated. However, it's kind of like drugs, where certain probiotics are good for particular conditions, but not something that you should take generally. And in the same way that you would expect for drugs, most people don't need to take most probiotics most of the time, or at least not the ones that have been studied so far. So, I think it's fair to say that public enthusiasm is greatly outstripping the actual evidence. But there is some evidence underlying that enthusiasm. TKF: Jeff, what about the future? Are we going to be able to cure diseases? Will I be able to speed up my microbiome's metabolism so I can eat ice cream and never gain an ounce? Miller: When you look at the probiotics that are out there, they date way back. They have their origins in food production, fermentation, cheese making, and other processes. So the question is, do they have a health benefit or not? And the results are often equivocal. But that's very different than looking at what we know now, and asking, okay, how would you engineer or reengineer this system? Would a small consortia of bacteria be a good way to decrease fatty tissue and increase muscle mass with diet? So, as Rob said, we haven't yet gotten to the point where we have applied our modern understanding of microbiomes to probiotics now in the marketplace. But the potential for doing that is definitely there. So, to answer your question, it could cure infectious diseases. A great example is Clostridium difficile-induced diarrhea, which is caused by antibiotics. The best cure that we know is fecal microbiome transplantation from a healthy donor. It is about 90 percent effective, so we know it can work. It's very crude, and so the question now is how to make it better through more refined science, rather than hit-and-miss empirical testing. Knight: It's important to remember that this is not just for the future. There are people walking around, alive now, who would be dead had they not received fecal microbiome transplants. This is really a current technology that works and is being clinically applied now. And what we need to do is to refine it. But it's not something that's in the future, it's something that's here today. [Body Bugs: 5 Surprising Facts About Your Microbiome ] TKF: This opens up some very interesting questions. One of the things we've discovered about the human microbiome is that it influences all kinds of things, from brain development and obesity to behavior. These are the very things that define who we are. Now we're talking about possibly synthesizing artificial microbiomes. This raises some ethical issues, doesn't it? Miller: Definitely. Ethics is a huge, huge area. "Do no harm" is the first principal, whether we're talking about permafrost, agriculture or the human gastrointestinal tract. And so, the requirements for reengineering microbiota to use as a drug have got to be stringent and carefully controlled. And safety, obviously, is going to be the first issue. But it's complicated, because these are dynamic systems. And the question is, how long will any changes last? What else would change the result of making these perturbations, etcetera? So we need to understand a great deal more before we try to engineer and manipulate at a large scale. TKF: Janet, you study ecology. Could you imagine a large scale ecological intervention using microbiomes? Jansson: Before I address that, I just want to go back to our earlier discussion about probiotics. In addition to changing our microbiome, we can also influence it through the food we put into it. This is also a strategy that is sometimes successful, though not very well understood. Instead of a probiotic, it’s called a prebiotic. For example, you can eat what is called a resistant carbohydrate or starch, which is not easy to digest. So it makes it to your intestine relatively intact. This allows the microorganisms in your gut to consume and ferment it, and that's beneficial for the colonic health. As for actually manipulating an ecosystem on a large scale, this is, of course, difficult. There have been people who have talked about fertilizing the oceans by adding iron, to buffer or mitigate the impact of increasing CO2 concentrations. But when it comes to permafrost, how to prevent the degradation of the carbon that is trapped there? That is difficult. But by gaining knowledge about the types of organisms that are there and the ones that become active when the permafrost does begin to thaw, we can at least predict the implications of those changes. Knight: Just to build on what Janet said, it's important to remember that we've already radically reengineered, through agriculture, both soil and human microbiomes over most of the planet. We're brought them into states that have no precedent in nature. The issue is that we didn't understand at all what we were doing or what our impacts on those microbiomes were. So, it's not that we can't change them. We are already changing them. And have already changed them. The question's more, "Can we change them in a more nuanced and directed way, where we have a better understanding of the ways that we can change them, at the microbiome level as opposed to the industrial or occupational level?" TKF: We've talked about microbiomes impacting out development and behavior. These are the things that determine our personality. For a long time, researchers thought that our genetic makeup determined these things. Do we understand the interaction between microbiomes and genome? Janet, you're shaking your head, so why don't you start. Jansson: I can tell you that this is a real hot area of research right now. My group and several other groups are trying to establish the link between the host's genome and the microbiome. I can say that preliminary evidence – there have been a few publications mainly looking at mouse models – suggest that there is a link. Rob's taken a more historical perspective, looking at different types of human populations and the impact of ancestral lifestyles on microbiomes. Rob, maybe you want to comment on that? Knight: Yes. We know that both in mice and in humans, lifestyle behaviors, like diet and hygiene especially, have had a much larger impact than host genetics. This is true, even though host genetics still has a highly statistically significant impact on particular features of the microbiome, including, interestingly, features that are associated with obesity in humans. Miller: To add one thing to what Rob said, we've coevolved with our microbial communities since long before we became Homo sapiens. We have only about a dozen genes in our genome to digest complex carbohydrates. The microbiota in our gastrointestinal tract brings hundreds of genes that do that for us. And so, when we eat a healthy high fiber diet, what we're really doing is relying on these microbial consortia to digest that food for us, so that we can take some of the products and use them for energy and other purposes. TKF: So, as one listener asks, maybe it's not such a great idea to use bactericides to kill microbes on every surface in our homes? Miller: Not a good idea for a lot of reasons. Rob, you shook your head, so I'll let you start. Knight: Well, it's bad for so many reasons. Both in terms of increasing antimicrobial-resistant bacteria, because the bacteria that survive your attempts to kill them can then spread those resistant genes to other bacteria that infect us directly. And also because there's evidence, increasingly, that keeping your house too clean increases the risk of autoimmune diseases, especially in children. TKF: We're drawing to the end of our discussion, so I want to ask you a final question. You know, our understanding of the microbiome has changed dramatically over the past 10 or 15 years. Tell me, what has surprised you most about what you have discovered? Janet, why don't we start with you? Jansson: I think the thing that has surprised me the most is the importance of the microbiome with respect to our health, in so many different ways. This was something that was not known at all just a decade ago. And so that's what I'll say. Knight: Links between the microbiome and behavior. A decade ago we had hints that the microbiome was linked to health. But no one predicted, at all, that it would have a key role in behavior, especially in mammals. Miller: Diversity. Microbes – whether you're studying pathogens, beneficial microbes, or microbes in any context – are enormously diverse. The concept of a species has to be reconsidered when you're talking about microbes, because they're not only diverse, but constantly exchanging genetic information. They are truly a constantly moving target, and the extent of their functional diversity is mind-boggling. TKF: Excellent. This is certainly an exciting time for microbial research. And I didn't even get to ask the best question, which is, “How does the microbiome in our gut determine our behavior?” Knight: We don't know how it happens, and that's why we need a Unified Microbiome Initiative. Follow all of the Expert Voices issues and debates — and become part of the discussion — on Facebook, Twitter and Google+. The views expressed are those of the author and do not necessarily reflect the views of the publisher. This version of the article was originally published on Live Science . Copyright 2016 LiveScience, a Purch company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

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SAN FRANCISCO (Reuters) - The following is a list of winners of the Breakthrough Prizes, worth $3 million each, announced on Sunday in Mountain View, California. Karl Deisseroth, Investigator of the Howard Hughes Medical Institute and the D.H. Chen Professor of Bioengineering and of Psychiatry at Stanford University, and Ed Boyden, Professor of Biological Engineering and Brain and Cognitive Sciences at the MIT Media Lab and the MIT McGovern Institute The two will each win a separate $3 million prize for developing and implementing optogenetics – the programming of neurons to express light-activated ion channels and pumps, so that their electrical activity can be controlled by light, potentially opening a new path to treatments for Parkinson’s, depression, Alzheimer’s and blindness. Helen Hobbs, Investigator of the Howard Hughes Medical Institute and a Professor of Internal Medicine and Molecular Genetics at the University of Texas Southwestern Medical Center Hobbs discovered human genetic variants that alter the levels and distribution of cholesterol and other lipids, inspiring new approaches to the prevention of cardiovascular and liver disease. Hardy discovered mutations in the Amyloid Precursor Protein gene (APP) that cause early onset Alzheimer’s. Svante Pääbo, Director at the Max Planck Institute for Evolutionary Anthropology Pääbo pioneered the sequencing of ancient DNA and ancient genomes, illuminating the origins of modern humans and our relationships to extinct relatives such as Neanderthals. Ian Agol, Associate Professor Department of Mathematics at University of California, Berkeley Agol contributed low dimensional topology and geometric group theory, including work on the solutions of the tameness, virtual Haken and virtual fibering conjectures. The prize will be shared among 1370 physicists representing five international teams, who will share $1 million, and their seven team leaders, who will share $2 million. The teams built technically challenging experiments in underground caves to trap the neutrino, and thereby confirmed the theory of neutrino oscillation. Super-Kamiokande, led by Takaaki Kajita of the Institute for the Physics and Mathematics of the Universe in Tokyo and Director at Institute of Cosmic Ray Research, and Yoichiro Suzuki, Daya Bay, led by Yifang Wang of the Institute for High Energy Physics and Kam-Biu Luk, Professor, Department of Physics University of California, at Berkeley K2K and T2K, led by Koichiro Nishikawa of K2K – from KEK to Kamioka – Long-Baseline Neutrino Oscillation Experiment SNO, led by Arthur B. McDonald, Director of the Sudbury Neutrino Observatory Institute

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