Events

Feb
6
Thu
2014
The Gut Microbiome: Health Improvment Beyond Energy Extraction
Feb 6 @ 12:00 pm – 1:00 pm

Image of Dr Rosa and John K Di Baise

Speaker(s): 
John K. Di Baise, M.D., Mayo Clinic, Department of Gastroenterology and Hepatology. Dr. Di Baise’s research interests relate to the diagnosis and treatment of gastrointestinal motility and nutrition-related disorders. Specifically,he focuses on the clinical utility of tests used in the diagnosis of motility disorders and the treatment of gastroparesis, chronic intestinal pseudo-obstruction, irritable bowel syndrome and short bowel syndrome.

Dr. Rosa Krajmalnik-Brown is currently an assistant professor in the School of Sustainable Engineering and the Built Environment and is part of the Swette Center for Environmental Biotechnology in the Biodesign Institute.

Location: Biodesign Auditorium

Web Cast:

Date & Time: February 6th, 2014 12:00 p.m.

Title: The Gut Microbiome: Health Improvement Beyond Energy Extraction

Abstract: 
Over the last decade, there has been an explosion in interest in the human microbiome both from the scientific community and the general public. This interest has been driven, in part, by the development of tools for identifying and studying the composition and functional capacity of microbes that coexist with the human host. Our gut harbors a complex community of over 100 trillion microbes that influence our normal physiology, metabolism and immune function. Disruption of this gut microbiome has been linked with a number of gastrointestinal disorders, metabolic disorders and immune-mediated conditions. In this presentation, we will provide an overview of the human microbiome focusing on the gut microbiome. We will then highlight research on the potential role of the gut microbiome in the development of obesity while also briefly reviewing its potential influence in the area of cancer. Finally, we will consider the manipulation of the gut microbiota as a potential option to treat disease.

Thank you and if you have questions please contact Chevas Samuels! And don’t forget, coffee will be served!

Chevas Samuels, Center for the Convergence of Physical Science and Cancer Biology

Arizona State University | P.O. Box 871504 | Tempe, AZ 85287

(480) 965-0342 | Fax: (480) 965-6362

Feb
20
Thu
2014
Epigenetics at the Interface of Aging, Exposures and Cancer
Feb 20 @ 12:00 pm – 1:00 pm

issa-con

Speaker(s):
Jean-Pierre Issa, MD is Professor of Medicine and Director of Temple University School of Medicine’s Fels Institute for Cancer Research and Molecular Biology. As principal investigator and project leader of several multi-million-dollar NIH/NCI-funded research projects, Dr. Issa has overseen ground-breaking studies. Particularly impressive are the important contributions his work has made to our understanding of epigenetics in the pathophysiology and treatment of cancer. His work has helped to reveal that different cancers arise along different molecular routes – predominantly genetic vs. predominantly epigenetic, an important concept in the pathophysiology of cancer. His focus on whole genome epigenetic studies has led to promising biomarkers for cancer detection, prognosis and prediction, and his proof-of-principle for epigenetic therapy of cancer is now standard of care in several types of leukemias.

Location:

Web Cast: Web Cast:

Date & Time: February 20th, 2014 12:00 p.m.

Title: Epigenetics At The Interface of Aging, Exposures and Cancer

Abstract:
The epigenome is reset during embryogenesis and matures around the end of development. Large scale genomic studies have now shown considerable proliferation dependent epigenome changes (drift) in aging cells (DNA methylation instability, chromatin instability). Comparison of rodent, primate and human aging shows that DNA methylation drift is conserved, depends primarily on chronologic age, and can be predicted to a certain degree by local genomic features (e.g. retrotransposons). It can therefore be argued that this epigenomic instability is a necessary result of the evolution of complex genomes that lack reprogramming capabilities in adult cells. Epigenetic drift creates gene expression variation in aging tissues that serve as an enabler of Darwinian evolution at the tissue level. Selective pressures result in cells with unique epigenetic programs that lead to diseases such as cancer or atherosclerosis. Importantly, epigenetic drift can be modulated by exposures (inflammation and perhaps diet), providing a mechanistic link between lifestyle and disease. In turn, epigenetic reprogramming could be useful for prevention and treatment of age-related pathology. In leukemias, reprogramming by DNA methylation inhibitors has gained acceptance as effective therapy for myeloid leukemias, and drugs for other epigenetic targets are rapidly proceeding towards clinical trials.

If you have questions please contact Chevas Samuels. Coffee will be served!

Chevas Samuels, Center for the Convergence of Physical Science and Cancer Biology

Arizona State University | P.O. Box 871504 | Tempe, AZ 85287

(480) 965-0342 | Fax: (480) 965-6362

Feb
22
Sat
2014
Complex Systems Theory and Cancer Biology
Feb 22 – Feb 23 all-day

tempe-feb-2014This Workshop will focus on understanding the nature of cancer in terms of the flow and control of information, and the activities of various regulatory and signaling networks in a systems context.

Topics will include GRNs, network theory applied to signaling pathways, chromosomal reorganization, systems biology, attractors, epigenetic landscapes, and thermodynamic and information theoretic aspects of stressed biosystems.

 

 


Group Photo II

Group Photo of the workshop participants

Paul and Pauline Davies

Paul and Pauline Davies

Dr. Sara Walker & Family

Dr. Sara Walker and family

Audio Interviews and Transcripts from the Workshop

Interview with Tim Newman

(Back to Audio)

Tim Newman: Well, we’re very excited about this project, so it’s probably the most exciting thing I’ve been involved in in my career. So, essentially, it started off with a coffee room discussion about what is robustness and my colleagues, I should just say who’s is involved in this; myself and then Julian Blow, who is a molecular biologist and Luca Albergante, who is a post doc with a background in computer science.
We were having a coffee one day a few years ago and got into an argument about what is robustness and how does it connect to evolvability, and Julian had this wonderful insight that somehow because cells are so complex and be described by so many parameters, the fact that they are robust means they can’t really, their robustness can’t depend on parameters, but he said the magic word that somehow it’s qualitative and then the whole project went off from there. And Luca found this theory from the 1960s that was written down by economists Ruppert and Quirk, called ‘Qualitative Stability,’ which basically says if you have a network – and they were thinking about a network of companies – is their particular shape they can have, so that it’s always stable, no matter how strong or weak the links are. And so we took this idea and applied it to gene networks and found that Ruppert and Quirk’s theory from economics actually holds in gene networks, which was a remarkable sort of application of one area of science to another. But because in biology, things evolve, we can take their theory a lot further, so that it’s not just a question of these gene networks obeying Ruppert and Quirk’s theory about having certain shapes that make them very stable, they also have to buffered against losing that stability through mutations and evolution.
So, we essentially have this buffered qualitative stability theory – in one sentence which is that gene networks are designed to be free of long loops and also to be buffered against getting long loops – and just from that one statement, you can make lots of predictions about what gene networks should look like and then we can test those predictions against gene networks that have been measured for bacteria and yeast and human cell lines and the remarkable thing is all the predictions that we make from this very simple theory are found to be true. So that’s very exciting.
Pauline Davies: Well, that’s just incredible because you know just superficially, who would ever have suspected it, but of course it does make sense, doesn’t it to give that stability?
Tim Newman: Absolutely and the reason I’m at this conference is because we did one final thing which was to then ask, “If we take a cancer cell line from a human cell line, does it satisfy the rules or not?” And we find, that whereas for e-coli and yeast and the non-human cancer cell line which obey all of these different predictions for stability, actually the cancer cell line breaks every rule. So, it’s really sort of the bad kid on the block and it’s clearly through evolution and the body giving up all of these very carefully created patents in the gene network, throwing them all away and becoming actually non-robust, and we think what this means is that it allows the cancer cells to be phenotypically plastic, so they can respond to all kinds of different environments in the body which would be a very strong survival strategy for cancer cells.
But I think the thing I’d like to stress is that this is a theory which has no parameters whatsoever and all the predictions are either just right or wrong, and so it’s been extremely exciting to find you can make a myriad of predictions where there’s absolutely no room for error, they’re either right or wrong, and we find in wild type cell lines and e-coli and yeast and so on, they’re all seem to be confirmed, so we really think we’re on to something about how gene networks are made.
Pauline Davies: Can there in the long term be any implications for treatment or prevention?
Tim Newman: I think it has actually because what I should say is that the, even though the cancer cell line that we studied breaks all of the rules, there’s only a handful of genes that are misbehaving in the network of hundreds of thousands of genes that actually cause the network to break these rules, and so by looking at buffered qualitative stability, you can immediately zoom in to a handful of genes that are sort of key players in disabling the cancer cells robustness, so this gives you a completely new way of thinking about targets. And what’s even more exciting is by removing just one or two genes from this handful; you can essentially resurrect the robustness of the cancer cell again. So, I think if one can look at the gene networks of cancer cells from different kinds of cancers, identify – assuming that they have these loops and break BQS – identify the genes that are misbehaving, it gives you a completely independent new way of identifying strong targets for gene therapy.
Pauline Davies: Well, you’d need to study even more networks, don’t you?
Tim Newman: So, yes, so basically this is an example now where the theory is ahead of the game. We’ve studied all of the data that is out there, so we just have to wait now for a year or two, hopefully experimentalists will get excited about this theory and accelerate the pace at which they are generating these transcription networks. But the theory is sitting there waiting to be wielded, and we’re just waiting now for these large teams to generate more networks.
Pauline Davies: Well congratulations.
Tim Newman: Thanks Pauline, it’s great to see you.

Interview with Christoph Adami

(Back to Audio)

Christoph Adami is a Professor of Microbiology and Molecular Genetics and a Professor of Physics and Astronomy at Michigan State University. He discusses his experience of the workshop.
Chris Adami: Even though I’m in the department of Microbiology and Molecular Genetics, I work mostly in evolution and mostly inside of the computer. So I’m a theorist and if you want to make progress in disease, for example, you need to know lots of details and there are some people here that do fantastic things with actual experimental systems, but also with computational and theoretical systems, and so for me, I can learn a lot of things here that I could not learn in my normal environment.
Pauline Davies: Can you pick anything out that has meant a lot to you?
Chris Adami: One of the talks today made the point that you can have adaptation in cancer cells and normal cells without any mutations and that’s something that I was kind of aware of but that I also tend to forget, because I work with mutations all the time. All this stuff that I do is with evolution is with mutations and that makes me forget about the fact that cells have the capacity to change their state as a function of environmental influences and then therefore that many of the things in the changes that we see in cancerous cells may actually not be mutation-related, so that was a good reminder for me.
Pauline Davies: Right. I know you were instrumental in some ways in setting up this PS-OC Network. Some of the initial conversations I believe were with you. So looking back at this, as an outsider really, because you haven’t’ been involved directly in the last five years, what do you think?
Chris Adami: I think first of all, that this was a fantastic idea to start these things. I wasn’t aware that throughout 30 years of research in cancer, so little progress has been made. As a theorist, it turns out that I like to think in fundamental terms and that not many people in cancer biology were doing that. And so, putting together cancer biologists and physicists and engineers and chemists, I think was a fantastic idea because the different cultures needed to interact. On the one hand, the physicists possibly did not have access to all the kind of clinical data that was necessary in order to make interesting theories and on the other hand, the clinical people did not have the kind of broad thinking that physicists would bring to the table. So, I think in the long run, it’s going to pay off handsomely. I think five years is probably too short a period to measure success. My hope is that these centers or other centers will go on.
Pauline Davies: Yes, I notice myself because I’ve been involved for the last five years, just seeing the level of discussion now that we have the physicists and their computers specialists and they’re giving some fairly very high-powered talks, but they’re bringing in biology that they might not have known about those years ago.
Chris Adami: Yes, I think that’s the key. When I talk to biologists, I have a very good biologist friend, and he always tells me, “I like talking to you because you are the kind of physicist that actually cares about details.” There are two kinds of physicists, those that care about the biological details and those that don’t. Those that don’t are useless for the biologists, so I mean these details matter. You cannot really build these types of theories in a vacuum; you need to have access to facts and very often, very, very detailed facts, and it is very often that minute, small details that perhaps even an experimentalist would overlook that end up making big breakthroughs, where somebody just looks at a fact and says, ‘Hmm, I wonder how we could understand that.’ It is in my view always the experiments and the facts that bring about new thinking. And in the absence of those, you’re just sitting in a room trying to imagine how the world is, and I don’t think that’s very successful.
Pauline Davies: Actually, that’s how major breakthroughs in physics have also occurred.
Chris Adami: That’s right. I don’t think what we’re doing here is dramatically different from how we’ve been doing it in physics, you know, when I was a graduate student in physics, I had the same type of approach. I always said ‘I need to look at data.’ Because in the absence of data, I don’t know what to even think about. I want to see data that nobody else has seen, data that is new, so that I can take a look at it, see the things that I understand and then see something that makes me stumble, and it is these type of things that open up new directions, because once you take a look at them and then you mull them over and you discuss them with other people and then at some point you might say, “You know what? I think I know where this comes from!” And then that’s where the beginning of research is. The beginning of research starts in my view, with data, with data that you don’t understand, but in order to have access to this kind of data, you have to have these collaborations that are being successfully put together by these PS-OC centers.
Pauline Davies: Thank you very much Chris.

Interview with Sui Huang

(Back to Audio)

Sui Huang is a professor and cancer researcher with a medical degree working at the Institute or Systems Biology in Seattle. He tries to understand cancer from very basic principles using a theoretical ‘landscape’ model first created by Conrad Waddington, the founder of systems biology.
Sui Huang: I think the biggest question I ask myself is “Why is it so hard to treat cancer?” I have given up trying cure or eradicate it, but first we need to understand why it is so hard to treat cancer. It is exactly the same as why is it so hard to fight the war against terrorists, because we never kill all of them – those that survive, they adapt very fast, not through a Darwinian evolution but predisposed to learn. You know when we kill 80% of terrorists in some way or cancer cells, the surviving ones are not innocent bystanders that just happened just to survive; they are not those that have mutations that make them more stronger and fitter but they actually adapt actively to the perturbation that we use to kill the other cells. But essentially it is a price we pay for a very complex development that we have evolved, and so it’s kind of a leftover, things that are not perfect.
Pauline Davies: And you have a very interesting way of describing it – you’re using a landscape, aren’t you, a landscape of possibilities with valleys and peaks and cancer evidently occupies some of the previously unoccupied valleys in that landscape.
Sui Huang: Yes, so that’s a metaphor that goes back to Waddington who uses landscape to describe development.
And the landscape gives us a lot of clues about that – the potential behaviors and the idea that when you treat cancer you have all those surviving cells and those are actually more malignant, and that’s all predicted by the landscape model. And then we move more and more towards new valleys, side valleys that are more and more away from the normal phenotype and so I think that’s a problem. It’s almost like entropy; we diversify them, we disperse them through this landscape and then they go through new states and new phenotypes. And we know now that this landscape can be computed based on the gene network and if we do so, then you will see you have many more potential cell types and we think that these potential never-occupied occupied cell types, when they are occupied, then they become cancer.
Pauline Davies: How did you come to find your model?
Sui Huang: It was a systematic search and I’m not the first. You know people previously suggested that cell types are these valleys in these landscapes and one can mathematically show that, and Stuart Kauffman proposed a long time ago that cancer cells could be those unoccupied attractors. And now we know, given what we know given about gene network, that there must be probably maybe many unoccupied attractor states. And that we also know that the beautiful thing about this is that it opens the possibility that you could get cancer without mutations and we have now a few examples of that, but mutations dramatically accelerate cancer.
Pauline Davies: How can you get cancer without mutations according to the landscape model?
Sui Huang: Essentially development is trying to go down to the lowest valleys and evolution has carved optimal paths to go down but, through some accidents you can get stuck further up in side valleys, so to speak. And to get to those side valleys there are all kinds of ways like, like toxins, carcinogens, mutagens and chronic injuries and stress can lead to cells being deviated from these highways down to the normal phenotypes. But mutations would just be a brutal deviation, so it’s much more likely to achieve that sort of mutation.
Pauline Davies: Does this landscape model have any predictive power?
Sui Huang: Yes, well it explains a lot of things. It is supposed to predict, and that was the old idea by Stuart Kauffman, that one should be able to apply differentiation therapy, try to differentiate cancer cells back to these normal valleys or high ways down to the normal state. And that has now become really popular with the idea of cancer stem cells, but it turns out that it is probably more difficult because once you’re in the side valleys, the path to the normal valleys is very, very rugged and so it’s probably harder than one thinks. So the qualitative properties of this is predicted this landscape model.
Pauline Davies: So do you think the main power in this landscape model is to show people from other disciplines just, where cancer might lie and the possibilities?
Sui Huang: So that was one original idea of visualization of very abstract ideas, but then it turns out that it’s much more useful than that, because if you have a landscape then that is a class of objects with its own properties, morphologies and that predicts a lot of constraints as to whether or not something is possible. So it’s more than a pedagogical visualization tool.
Pauline Davies: And what about any use in, giving clues for treatment in the future?
Sui Huang: The landscape would be useful if you know everything about molecular details of the gene network. Once you have that, then the idea of landscape will be very useful. As of now, we have just a more qualitative model that stimulates new ideas, for example, one is that a lot of this chemotherapy or attempts to kill tumors actually makes it worse, so you go farther away from the normal valleys.
Pauline Davies: Well thank you very much.
Sui Huang: Thank you.

Interview with Carol MacKintosh

(Back to Audio)

Interview with Carol MacKintosh

(Back to Audio)

Carol MacKintosh: So, we don’t have a name for the ancestor, but a modern day animal that’s similar to it is called ‘amphioxus’ or ‘lancelet’ and the remarkable thing is that the ancestor, which lived in the Cambrian Oceans, underwent a dramatic genetic event when all of the DNA duplicated and then later it all happened again. And somehow, these duplications give rise to a new species of animal and that new species became the ancestor of all of us, all of the back-boned animals; the fish, the birds, mammals, including humans.
Pauline Davies: And the animal, what does it look like?
Carol MacKintosh: Well, you would recognize it as a relative, so it’s like us in terms of having a neural tube, muscle blocks, it has structures called pharyngeal arches, where we have facial structures and it has a post anal tail. But, of course it doesn’t have all of our fine features, it doesn’t have a big brain, it has no bones, it’s heartless and so, that is how it differs from the vertebrae animals
Pauline Davies: Okay and so this very primitive animal, it started doubling its chromosomes?
Carol MacKintosh: Yes, actually, doubling of chromosomes is quite common in nature, particularly well-known in plants, but it has only recently realized that such an event happened in our own ancestry and the remarkable things as far as I’m concerned is that the progeny survived, you know, despite this massive change in doubling of the DNA , and it all happened again in a later generation.
Somehow, the babies, survived and became our ancestor.
Pauline Davies: So I think you’re saying we, well the animals that followed this primitive organism that used to live in the sea, had eight copies of each chromosome, am I correct?
Carol MacKintosh: The original ancestor had a pair of each chromosome and then that doubled, so they had four, and that doubled so they had eight. But, then of course, during this process and afterwards, there were lost of losses of parts of chromosomes and individual genes, so in modern day humans, this has been incorporated so that we’re back to two, but we have copies that are scattered throughout the genome, that are what was retained from that time.
Pauline Davies: It’s really a remarkable story.
Carol MacKintosh: Well the discovery was made, I guess, in 2008 when the sequence of the modern day amphioxus that resembles the ancestor, its genome was compared with that of humans and that was when it really became established. Before that, various lines of research had indicated that this was a possibility.
Pauline Davies: And now you think that these spare copies of genes that we’ve got are somehow implicated in cancer?
Carol MacKintosh: Well, yes, so what we discovered in my research group is that the extra copies, so having two or three or four of particular genes, what this has really done is its given a real boost to the communication systems in our bodies.
So what we’ve discovered is that these copies form little teams, families. and these families operate in networks inside our cells and because of the way that they work in this team way, what this means is that cells in our bodies are able to transmit lots of different messages from the hormones that control our cells, and they do this in a way, it’s kind like Smartphones. You know, what’s special about smartphones is that they can integrate multiple messages and make sense of them and cells in our body are better at integrating multiple messages than even the smartest of smartphones.
Pauline Davies: And that’s because we’ve got the spare capacity, the duplication.
Carol MacKintosh: Yes! Having extra copies means you can pick and choose and make up different transmission routes for messages, but the cancer issue comes when, because of these sophisticated systems that were required to make the vertebrae animals, the down-side of that is when the communication systems go wrong – because of the sophistication of these systems it can go wrong – that can give rise to cancer.
Pauline Davies: And what is the purpose in the normal individual in having so many signaling pathways?
Carol MacKintosh: Well, cancer becomes reliant on signals that tell the cancer to grow and divide and proliferate. Now these same pathways are required at certain points during our development, so for example, as an embryo, its essential that these pathways that tell cells to grow and proliferate, they have to be switched on in a very controlled way and the right cells at the right time to allow the organism to grow and develop. But in the adult, for example, what happens is the cancer cells become very dependent on these pathways, whereas rest of the body only requires these pathways at certain times, for regenerating, you know, various organs and so on.
Pauline Davies: Wound healing?
Carol MacKintosh: Yes, wound healing for example. But so the cancers have a greater reliance on the signaling pathways that tell it to do that particular thing, whereas the rest of the body is operating using different signaling pathways that are telling different cells in our bodies to do different things at different times.
Pauline Davies: And I think that you are implying, or saying, that 60% of cancers had one of these families implicated, where you have multiple copies.

Mar
6
Thu
2014
Exploring the Microbial World
Mar 6 @ 12:00 pm – 1:00 pm

t100_wolfe

Speaker(s):
Dr. Nathan Wolfe, founder and CEO of Global Viral Forecasting has degrees in human biology, biological anthropology, and immunology and infectious disease from Harvard University and Stanford University. He has been a professor of epidemiology at Johns Hopkins University and UCLA, and is now a visiting professor of human biology at Stanford in addition to directing Global Virus Forecasting.
Dr. Wolfe explores for harmful viruses in remote places and uses his field sites around the world as “listening posts” to try to intercept viruses before they spread widely. Many viruses, like HIV and influenza, jumped from animals to humans, so Dr. Wolfe works in villages whose inhabitants rely on wild game, or bushmeat, for protein. When hunters contact animal fluids during butchering, it makes them especially vulnerable to hosting new microbes. By collecting thousands of blood samples, hunters are important allies for studying emerging diseases.

Location: Biodesign Auditorium

Web Cast: View Event Online
NOTE: This web cast will be available only during the live stream presentation. It will not be posted later. We are sorry for any inconvenience.

Date & Time: March 6th, 2014 12:00 p.m.

Title: Exploring the Microbial World

Abstract:
Most of the diversity of life on earth is contained within the genomes of the planet’s microbes, including bacteria and particularly viruses, which infect every known form of cellular life on the planet. Arguably the most important biological realm for exploration is the microbial world on earth. Exploration within the microbial world has the potential to generate solutions to some of the major problems and mysteries on our planet, including the future of pandemics, the origins and causes of cancer, and the fundamental boundaries and limits of life. In this seminar, I will discuss contemporary exploration in the microbial world with particular emphasis on the activities done in my own research group on viral discovery and diversity.

Thank you and if you have questions please contact Chevas Samuels! And don’t forget, coffee will be served!

Chevas Samuels, Center for the Convergence of Physical Science and Cancer Biology

Arizona State University | P.O. Box 871504 | Tempe, AZ 85287

(480) 965-0342 | Fax: (480) 965-6362

Mar
20
Thu
2014
How Bacteria and Cancer Cells Regulate Mutagenesis and Their Ability to Evolve
Mar 20 @ 12:00 pm – 1:00 pm

Susan RosenbergFinal

Speaker(s):
Susan M Rosenberg, PhD, Ben F Love Chair in Cancer Research, Professor, Departments of Molecular and Human Genetics,
Biochemistry and Molecular Biology, and Molecular Virology and Microbiology. Dr. Rosenberg is also head of the Cancer Evolvability Program at The Dan L Duncan Cancer Center.

Title: How Bacteria and Cancer Cells Regulate Mutagenesis and Their Ability to Evolve

Webcast:

Abstract:
Our concept of a stable genome is changing from one in which the DNA sequence is passed faithfully from generation to generation to another in which genomes are plastic and responsive to environmental changes. Growing evidence shows that environmental stresses induce mechanisms of genomic instability in bacteria, yeast, and human cells, generating occasional fitter mutants and potentially accelerating evolution and disease. The emerging molecular mechanisms of stress-inducible mutagenesis vary but share telling common components that underscore two common themes of the non-randomness of mutation: (1) regulation of mutagenesis in time by cellular stress responses, which promote mutations specifically when cells are poorly adapted to their environments—i.e., when they are stressed; (2) restriction of mutagenesis in genomic space causing mutation hotspots, clusters and showers. Mutational hot-spotting may target specific genomic regions and allow local concerted evolution (adaptive evolution requiring multiple mutations). This talk will focus on a molecular mechanism of stress-induced mutation in E. coli and note its parallels in other organisms including human cancer. The mechanism is a stress-response-orchestrated switch to error-prone repair of DNA breaks. We consider its regulation by stress responses, demonstrate its formation of mutation hotspots near DNA breaks, and report our discovery of a large gene network that underlies mutagenic repair of DNA breaks, more than half of which functions in stress sensing and signaling. The data show the importance of stress-response control and also that biological functions of large fractions of networks can be understood when molecular mechanisms are considered and functional studies employed. Regulation of mutagenesis in time and genomic space is widespread in many organisms and circumstances. Such mechanisms may fuel biological evolution and genetic disease, including pathogen-host adaptation and drug resistance and tumor and other disease progression and resistance mechanisms, much of which occurs under stress, driven by mutations.

Dr. Rosenberg’s research interests include Genome Instability in Evolution, Antibiotic Resistance, Cancer, Stress-Induced Mutagenesis, Antibiotic-Resistance Mutation, Spontaneous DNA Damage and From Bacteria to Humans: Genomic-Caretaker Proteins and Cancer.

Location:
View Event Online

If you have questions please contact Chevas Samuels. And don’t forget, coffee will be served. Thank you.

Chevas Samuels, Center for the Convergence of Physical Science and Cancer Biology

Arizona State University | P.O. Box 871504 | Tempe, AZ 85287

(480) 965-0342 | Fax: (480) 965-6362

Mar
24
Mon
2014
Challenging the Dogma: A New View of the Genomic Programming of Complex Organisms
Mar 24 @ 12:30 pm – 1:30 pm

john_mattick photo

Speaker(s):
Dr. John S. Mattick is the Director of The Garvan Institute of Medical Research in Sydney, Australia.After completing his undergraduate and postgraduate studies at the University of Sydney and Monash University in 1977, he undertook postdoctoral training at Baylor College of Medicine in Houston, Texas. In 1982 he returned to Australia to work at the CSIRO Division of Molecular Biology in Sydney, and in 1988 moved to the University of Queensland in Brisbane, where he was the Foundation Professor of Molecular Biology, and Foundation Director, ARC Federation Fellow and then NHMRC Australia Fellow at the Institute for Molecular Bioscience.
Professor Mattick has served on councils, advisory boards and committees of a number of research and funding organisations, including Genome Canada, the Wellcome Trust, the Human Frontier Science Program, the National Health & Medical Research Council, and the Human Genome Organisation.
Over the past 20 years he has pioneered a new view of the genetic programming of humans and other complex organisms, by showing that the majority of the genome, previously considered ‘junk’, actually specifies a dynamic network of regulatory RNAs that guide differentiation and development. He has published over 250 research articles and his work has received coverage in Nature, Science, Scientific American, New Scientist and the New York Times, among others.

Location: Biodesign Auditorium

View Event Online:

Date & Time: March 24, 2014 12:30 p.m.

Title:Challenging the Dogma: A New View of the Genomic Programming of Complex Organisms

Apr
17
Thu
2014
Cracking The Bioelectric Code: Taming the Voltage-Based Language Of Cells to Re-grow Whole Organs and Normalize Cancer
Apr 17 @ 12:00 pm – 1:00 pm

levin

Speaker: Mike Levin is the Director of Tufts Center for Regenerative and Developmental Biology, focusing on morphological and behavioral information processing in living systems

Location: Biodesign Auditorium

Web Cast: THERE WILL NOT BE VIDEO AVAILABLE FOR THIS LECTURE

Date & Time: April 17th, 2014 12:00 p.m.

Title: Cracking the Bioelectric Code: Taming the Voltage-Based Language of Cells to Re-grow Whole Organs and Normalize Cancer. 

Abstract:
Many species of complex animals are able to regenerate entire organs. Our lab studies show that electric gradients control cell proliferation, migration, and differentiation, while bioelectrical signals serve as master regulators of tissue patterning. Molecular-level changes in bioelectric state can initiate complete development of eyes, brains, hearts, limbs, and spinal cords, as well as normalize neoplastic growth. Genetics and bioelectricity thus constitute parallel but interacting layers of biological control, a discovery with sweeping implications for cancer management, regenerative medicine, synthetic biology and bioengineering.

 

If you have questions please contact Chevas Samuels! And don’t forget, coffee will be served!

Chevas Samuels, Center for the Convergence of Physical Science and Cancer Biology

Arizona State University | P.O. Box 871504 | Tempe, AZ 85287

(480) 965-0342 | Fax: (480) 965-6362

Cancer: The Beat of An Ancient Drum – Paul Davies
Apr 17 @ 7:00 pm

 

4929_BeyondWOC_fullr_webAbstract
In this lecture Paul Davies will bring a physicist’s perspective to bear on the subject of cancer, by asking the big questions: Why does cancer exist? What are its deep evolutionary origins? How does it relate to embryogenesis? He will outline a provocative new theory of cancer as an evolutionary throwback, and discuss its profound implications for novel forms of therapy aimed at targeting cancer’s weaknesses rather than its strengths.

About the Speaker
Paul Davies is Director of The Beyond Center for Fundamental Concepts in Science and Principal Investigator for the National Cancer Institute’s Center for the Convergence of Physical Science and Cancer Biology, both at Arizona State University. He is a theoretical physicist, cosmologist and astrobiologist with research experience ranging from the origin of the universe to the origin of life. He is noted for his work on the theory of quantum fields in curved spacetime, black holes, early-universe cosmology, the arrow of time, the nature of the laws of physics and the emergence of life in the universe.

Webcast:

May
1
Thu
2014
Rare Events with Large-Impact: Bioengineering & Clinical Applications of Circulating Tumor Cells
May 1 @ 12:00 pm – 1:00 pm

mehmettoner

Speaker(s):
Mehmet Toner, PhD is Professor of Surgery (Biomedical Engineering) at the Massachusetts General Hospital, Harvard Medical School, and is the founding director of the NIH BioMEMS Resource Center. Dr. Toner is internationally recognized for his multidisciplinary approach to biomedical problems in the areas of low-temperature biology and biostabilization, tissue engineering and artificial organs, and microsystems bioengineering in clinical medicine and biology.

Location: Biodesign Auditorium

View Event Online:

Date & Time: May 1st, 2014 12:00 p.m.

Title: Rare Events with Large-Impact: Bioengineering & Clinical Applications of Circulating Tumor Cells

Abstract:
Viable tumor-derived circulating tumor cells (CTCs) have been identified in peripheral blood from cancer patients and are probably the origin of intractable metastatic disease. However, the ability to isolate CTCs has proven to be difficult due to the exceedingly low frequency of CTCs in circulation. We introduced several microfluidic methods to improve the sensitivity of rare event CTC isolation, a strategy that is particularly attractive because it can lead to efficient purification of viable CTCs from unprocessed whole blood. The micropost CTC-Chip (μpCTC-Chip) relies on laminar flow of blood cells through anti-EpCAM antibody-coated microposts, whereas the herringbone CTC-Chip (HbCTC-Chip) uses micro-vortices generated by herringbone-shaped grooves to efficiently direct cells toward antibody-coated surfaces. These antigen-dependent CTC isolation approaches led to the development of a third technology, which is tumor marker free (or antigen-independent) sorting of CTCs. We call this integrated microfluidic system the CTC-iChip, based on the inertial focusing strategy, which allows positioning of cells in a near-single file line, such that they can be precisely deflected using minimal magnetic force. We applied these three microfluidic platforms to blood samples obtained from lung, prostate, breast, colon, melanoma, and pancreatic cancer patients. We isolated CTCs from patients with metastatic non-small-cell-lung cancer and identified the EGFR activating mutation in CTCs. We also detected the T790M mutation, which confers drug resistance. We also applied microchip to isolate CTCs from blood specimens of patients with either metastatic or localized prostate cancer, and showed the presence of CTCs in early disease. Remarkably, the low shear design of the HBCTC-chip revealed micro-clusters of CTCs in a subset of patient samples. Microscopic CTC aggregates may contribute to the hematogenous dissemination of cancer. More recently, we used microfluidic capture of CTCs to measure androgen receptor (AR) signaling readouts before and after therapeutic interventions using single-cell immunofluorescence analysis of CTCs. The results support the relevance of CTCs as dynamic tumor-derived biomarkers, reflecting “real time” effects of cancer drugs on their therapeutic targets, and the potential of CTC signaling analysis to identify the early emergence of resistance to therapy. We also characterized epithelial-to-mesenchymal transition (EMT) in CTCs from breast cancer patients. While a few primary tumor cells simultaneously expressed mesenchymal and epithelial markers, mesenchymal cells were highly enriched in CTCs, and most importantly, serial CTC monitoring suggested an association of mesenchymal CTCs with disease progression suggesting a role for EMT in the blood-borne dissemination of human breast cancer. This presentation will share our integrated strategy to simultaneously advance the engineering and microfluidics of CTC-Chip development, the biology of these rare cells, and the potential clinical applications of circulating tumor cells.

If you have questions please contact Chevas Samuels. Coffee will be served!

Chevas Samuels, Center for the Convergence of Physical Science and Cancer Biology

Arizona State University | P.O. Box 871504 | Tempe, AZ 85287

(480) 965-0342 | Fax: (480) 965-6362

Jul
29
Tue
2014
Paul Davies Lecture: Six Big Questions at the Frontiers of Science
Jul 29 @ 6:00 pm – 7:30 pm

Screen shot 2014-07-28 at 3.19.05 PM

Speaker(s):
Paul Davies is a theoretical physicist, cosmologist, astrobiologist and best-selling author. He is Regents’ Professor and Director of the Beyond Centre for Fundamental Concepts in Science, co-Director of its Cosmology Initiative, and Principal Investigator in the Centre for the Convergence of Physical Science and Cancer Biology, all at Arizona State University.
Davies’ research interests are focused on the “big questions” of existence, including the origin of the universe, the origin of life, the nature of time and the search for life in the universe. In addition to his research, Davies is known as a passionate science communicator. He has lectured on scientific topics at institutions as diverse as The World Economic Forum, the UN, Google, Windsor Castle, The Vatican and Westminster Abbey, as well as academic establishments such as The Royal Society, the AAAS and hundreds of universities. He has contributed to numerous debates about science, religion and culture and won the Templeton Prize in 1995.

He has written 28 popular and specialist books including bestsellers The Mind of God, How to Build a Time Machine, and The Goldilocks Enigma. His latest book, The Eerie Silence, is about the search for intelligent life in the universe. Davies devised and presented a highly successful series of 45 minute BBC Radio 3 science documentaries, and a one-hour television documentary about his work in astrobiology, entitled The Cradle of Life. In Australia his many television projects included two six-part series The Big Questions, filmed in the outback, and More Big Questions.

Abstract:
From the origin of the universe to the nature of consciousness, scientists have grappled for centuries with the fundamental questions of existence. Now, in our time, huge progress is being made on many of the puzzles and paradoxes that fascinate all mankind.

In this unique and provocative lecture, renowned physicist and cosmologist Paul Davies will explain the most challenging questions at the frontiers of science – from the cosmos to cancer, from life’s murky beginnings to the search for ET.

ONLINE REGISTRATION PREFERRED

The UNSW Bookshop will be selling Paul’s books and he will be available after the lecture to sign copies.