Dr. Jeffrey Gordon is leading the field of Human Metagenomics with his work on the Human Microbiome
Host: Marc Pelletier
Guest: Dr. Jeffrey Gordon
In episode 9, which was our first episode on the field of Metagenomics, I teased Dr. Ed Delong (MIT) a little. Ed samples bacteria from the depths of the Pacific ocean about 100 miles off the north cost of Hawaii and sequences their entire genomes, revealing enormous amounts of information about the microbial communities living there. I suggested to him that it might be easier to study microbial community genomics by sampling from puddles outside the lab in Cambridge Massachusetts...
Well, our guest today looks even a little closer than that puddle. Dr. Jeffery Gordon is a Professor of Gastroenterology, the Director of the Center for Genome Sciences, and the Head of the Department of Molecular Biology and Pharmacology at Washington University in St-Louis. He is also leading one of the most interesting and important metagenomics projects today, the Human Microbiome.
Some interesting links:
RUNNING TIME: 1:12:12
Leo and I explore the world of NanoBiotechnology with Peter Searson and Denis Wirtz from Johns Hopkins
I was going through my hard drive and I stumbled on a large audio file. It was one of the LOST EPISODES!!! I had actually made a backup! So here it is... I apologize to our guests, who must have thought we were crazy, but they have been really good sports about this. They are doing some outstanding work, developing an area of biotechnology that brings together the best of materials science with biotechnology, focusing on medical applications. I certainly hope to have both Peter Searson and Denis Wirtz back on the show soon, and I promise not to lose the file this time!
A panel of leading scientists (and an engineer!) make predictions on the future of biotechnology
Host: Marc Pelletier
Dr. John Bergeron, Professor and Chair of the Department of Anatomy and Cell Biology at McGill University, and former President of the Human Proteome Organization (HUPO), and founder of Caprion Proteomics
Dr. Drew Endy, Cabot Assistant Professor of Biological Engineering at MIT, in Cambridge Massachusetts
Dr. Edward Delong, Professor, Division of Biological Engineering & Department of Civil and Environmental Engineering at MIT
Leo (our Chief TWiT) often mentions Ray Kurzweil's hypothesis of a singularity. Kurzwell writes that "Within a few decades, machine intelligence will surpass human intelligence, leading to The Singularity—technological change so rapid and profound it represents a rupture in the fabric of human history". This prompted me to think about what is currently going on in biotech: James Watson (Nobel Laureate that shared the prize for solving the structure of DNA) recently received a copy of his OWN genome. Also, scientists are developing drugs that could extend the human life span by thirty years (Ep. 2), and moreover, engineers are now considering biology to be a substrate for engineering: producing artificial chromosomes (Ep. 9) in the lab. These amazing developments raise the question of a singularity in biotechnology. Is the time approaching where we will have a --complete-- understanding of the underlying processes of life? If so, how will this change our health, medicine, our lives?
It is clear that our greatest challenges still lie ahead: cancer, heart disease, HIV-AIDS, organ regeneration, environmental change etc... But the fact remains: technologies are advancing at logarithmic rates, and biotechnology is no exception. So for this episode, I sought out three world leading scientists (and engineer!) to discuss the current state of biotechnology, and what we should expect in this century- the century of biotech...
DISCLAIMER: I had some difficulties with the audio from Canada. I struggled with Skype and Dr. Bergeron's bandwith and levels were low but audible. Since I didn't see it in the stars to be able to pull together this level of panelists again soon I went ahead with the recording. When I boosted his audio in post production, noise was also amplified and difficult to remove. Fortunately Ryan Leng from Pulau Pinang, Malaysia, did some great work improving clarity and listenability.
It is not every day that we get to speak with someone who's work has been so pivotal that it has directly ushered in a new technological era.
As you may know from listening to this netcast, what we are really trying to do is get is an understanding of how life works and what it means to be human, down to the molecular level. To answer this question, scientists around the world have embarked on genomic projects that enable us to to compare our genome to that of bacteria, mice, worms, chimpanzees, and even to our closest evolutionary relative, the Neanderthal. Our guest, Dr. Leroy Hood, has made this possible: and it is not an understatement to say that his inventions have truly enabled molecular biology. A few decades back he invented among other things-- the DNA sequencer-- and the incredible new era of genomics had began.
Dr. Larry Smarr discusses the future of computing and the internet...
Guest: Dr. Larry Smarr is the Director of the California Institute for Telecommunications and Information Technology (CalIT2)
Dr. Smarr has made enormous contributions to both supercomputing and the internet as we know it today. As you will find out - he could just as comfortably been a guest on any of the other TWiT netcasts including This Week in Media, Windows OR MacBreak Weekly, the Tech Guy, or even FLOSS Weekly. Dr. Ed Delong -- our guest from FiB Episode 9 suggested that he would be an excellent guest for his contributions to the cyberinfrastructure that is enabling the emerging field of metagenomics. Well, our discussion with Dr. Smarr goes far beyond metagenomics and biotech...
Scott Johnson and Robert Miller talk about the approaches used by Myelin Repair Foundation (MRF) to accelerate discovery...
Hosts: Marc Pelletier
Guests: Scott Johnson is the President and Founder of the The Myelin Repair Foundation, and Dr. Robert Miller is a Principal Investigator with the MRF and Professor of Neurosciences at Case Western Reserve University School of Medicine in Cleveland OH.
Scott, Robert, and four more great neuroscientists with the MRF have taken on one the great medical challenges our time -Multiple Sclerosis (MS). They have developed and trademarked an exiting new approach to R&D called ARC, for Accelerated Research Collaboration, which they are applying to MS. Scientific American recently recognized Scott as one the top 50 leaders in science, business, and policy, and this model has been featured in "The Definitive Drucker" a biography of "ideas" of the business management icon Peter Drucker. By combining highly effective approaches to management and collaboration, with best minds in the fields of neuroscience and myelin repair, they are on a trek to conquer MS.
If you would like to make a donation toward curing MS please visit The Myelin Repair Foundation.
Dr. John Bergeron describes how proteomics could revolutionize modern medicine...
Guests: Dr. John J. Bergeron is Professor and Chair of the Department of Anatomy and Cell Biology at McGill University, and former President of the Human Proteome Organization (HUPO), and founder of Caprion Proteomics
John has just completed his tenure as president of the Human Proteome Organization (HUPO). He explains how the science of proteomics is bringing us toward a COMPLETE understanding of the human anatomy down to the molecular (protein) level. We are moving toward a new level of molecular medicine with a near atomic "atlas" of the human body. Diagnosing cancer could eventually be done using a minute sample of blood, and earlier than ever imagined, by simply looking at protein profiles. It is clear that any conversation about biotechnology must inevitably include proteomics...
Drs. Paabo and Jarvie talk about the Neanderthal Genome Sequencing Project...
In this episode, Dr. Svante Paabo explains how he isolates the ancient DNA of Neanderthals from museum specimens. He is leading the team that is using this material to sequence the entire Neanderthal genome, which should take just over two years. By comparing our genome to that of the Neanderthals, great light will be shed on what it means to be human.
Here is where it gets interesting: If you remember in episode 8, we spoke with Dr. Drew Endy (MIT) about how synthetic biology will allow us to synthesize the human genome from using machines within ten years. This means that we could theoretically see the RETURN OF THE NEANDERTHAL in a decade, not that anyone intends on bringing back the Neanderthal ;)
I chatted with Dr. Endy yesterday to ask him about the likelihood of this, and he added that it would probably cost too much in ten years time, but would be very cheap in twenty...
Dr. Carla Shatz explains the mechanisms used by the developing brain to assemble into a neuronal network...
Guest: Dr. Carla Shatz, Department Chair and Nathan Marsh Pusey Professor of Neurobiology, Harvard Medical School
Imagine if there was a computer with a multi-core CPU that could self-assemble? And rather than a 64 bit bandwidth, it was 10,000 bit and had access to several terabytes of ram? And more incredibly, all of this could fit into a TWiT beenie? Perhaps, drawing a comparison between the human brain and a computer is a little unfair since silicone based processors cannot yet self-assemble ; )
In this episode, Dr. Shatz generously shares her expertise with us. She describes how the human brain establishes connections between well over a hundred billion nerve cells with great precision; how this wiring happens during development. Shatz has made great contributions to our understanding of this process and her work will undoubtedly lead to major therapeutics in areas of neurodegenerative and neuromuscular diseases, spinal cord injury, and much more. Dr. Shatz is leading the field at one of the most important frontiers of science today.
Dr. Ed Delong explores the seas for novel genes and genomes...
Guest: Dr. Edward F. Delong, Professor, Division of Biological Engineering & Department of Civil and Environmental Engineering at MIT
Our guest, Dr. Ed Delong, studies complex microbial communities in the Pacific ocean off the coast of Hawaii. In our discussion, he explains how genomics not only reveals important details on the nature of these marine microbes, but can also uncover genetic, biochemical, and even metabolic information with great potential for the development of new technologies, providing novel building blocks for synthetic biologists or genetic engineers. While seeking a better understanding of life in the oceans, Delong is extending our knowledge of the living world and discovering new genes in a way that is not unlike combing the tropical rainforests for new species.
I would like to point out that we record these netcasts using Skype, and the bandwidth at MIT is either pretty slim, or heavily abused. So at one point we switch over to the phone lines, which actually worked out pretty well.
Dr. Drew Endy develops tools for engineers to design and build living organims...
In this episode, Leo and I discuss the emerging field of Synthetic Biology with our guest Dr. Drew Endy. Dr. Endy is the Cabot Assistant Professor of Biological Engineering at MIT. A quote from him outlines well the topic of today's discussion:"We’re going from looking at the living world as only coming from nature, to a subset of the living world being produced by engineers, who design and build hopefully useful living artifacts according to our specifications" (MITWorld).
This means that biotechnology is in a transition. Not only will molecular biologists continue to dissect the genome to improve our understanding of a living organism, but the parts (or genes) will be used to engineer novel organisms for a desired purpose or novel use. Synthetic biology is to genetic engineering what Web 2.0 is to the internet. This is truly biotech of the 21st century...
PLEASE BEAR WITH US TOWARDS THE END OF THE INTERVIEW, as Dr. Endy's audio breaks up a little. We record these netcasts using Skype, and as you would expect, the bandwidth is heavily used by the faculty, staff, and students at MIT.
One of the greatest quests in science is to find a vaccine to prevent HIV infection. The human toll of HIV/AIDS is astonishing, with more than 25 million men, women, and children having died from AIDS. Approximately 40 million people are living with HIV and there are an estimated 5 million new infection per year.
Just over twenty years ago, Dr. Desrosiers made a pivotal discovery: the Simian Immunodeficiency Virus (SIV) It is the closest known relative to HIV, and has provided one of the best tools to study the biology of HIV and related viruses. This animal model to HIV has allowed scientists to perform experiments that are simply impossible to do on humans. Ever since his discovery of SIV, Dr. Desrosiers has been endeavoring to understand all aspects of both SIV and HIV, and working tirelessly towards a vaccine.
For more on Dr. Desrosiers' work please visit the the New England Primate Research Center
NOTE: We sincerely apologize for the audio quality. While it was a very difficult mix, there was no question that Dr. Griffith's visionary work was worth sharing!
While we probably won't see any replicants (Blade Runner) seeking world domination any time soon, we really are at a crossroads of science fiction and biotechnology. Dr. Griffith is a leader in the field of tissue engineering: a field that seeks to develop replacement organs and tissues, and also provide an unlimited supply of living human organs for scientists to use to better understand disease and develop new therapies.
Dr. Griffith has chosen to tackle the latter approach. By providing a high fidelity system in which to study organ function and disease, she is accelerating the pace of drug/therapeutic development. In doing so, cures could become available to patients before they get to the point of organ failure and the need for transplant surgery.
I was lucky enough to be invited by Dr. David Brodbeck to be a guest on his podcast - Thunderbird Six. We talk a little about the history of FiB and working with Leo...
It was a blast!
Dr. Andre Nantel explain how we can capture a picture of the genome in action
In this episode, we talk about how microarrays are revolutionizing biomedical sciences. Just ten years ago, all genetic and biochemical experiments were performed on a scale of one to a few genes (DNA) or proteins at a time. Now with the advent of microarrays, hundreds of thousands of DNA or protein samples can be analyzed in parallel experiments (side by side on a chip) in a matter of hours. Where once we could only determine whether or not the expression of a single gene was turned on or off using a technique called northern blotting, the dynamic interplay of an entire genome in response to environmental cues or disease states can be monitored in a single experiment. We are slowly transitioning to a new era of individualized medicine, where preventive or therapeutic approaches will be tailored specifically to each individual.
You'll find André's picture of a DNA microarray being printed here, and an image of a DNA microarray in a scanner. Great shots André! He is an excellent photographer. His photoblog Digital Apoptosis is certainly worth a visit.
About Dr. Nantel:
Andre Nantel, M.Sc., Ph.D.
Research Officer, National Research Council of Canada
André Nantel is a Research Officer and Project Manager of the Microarray Lab at the NRC Biotechnology Research Institute in Montreal. He is also an Adjunct Professor at the Department of Anatomy and Cell Biology of McGill University. His group runs a facility for the design, production and utilization of DNA microarrays and he is part of an international effort that recently completed the final assembly and annotation of the genome of the fungal pathogen Candida albicans. He is also involved in the interpretation of a large number of transcriptional profiling projects in the fields of cancer research, molecular diagnostics and pathogenesis. Outside of DNA microarrays, his current research interests include the study of signal transduction pathways in cancer, more specifically the roles of adapter proteins in the modulation of kinase cascades. The BRI's Microarray laboratory provides microarrays to academic and research groups worldwide as well as private companies in Canada. The laboratory also assists NRC Genomics research projects and collaborators from academia or the industry.
Part II - Interactome Networks (maybe we should call it Geno-Web 2.0?)
In the last episode, Dr. Vidal described the genome as a parts list. He and his team, at the Dana Farber Cancer Institute, have undertaken the major challenge to find out how these parts fit together. They have genetically engineered yeast strains to make complete sets of parts, pairwise, to see if they interact. This enormous endeavor has been termed the "Interactome".
Here, he explains how to make sense of such enormous data sets, that describe thousands upon thousands of interactions between proteins. His approach is to examine these interactions using methods similar to those used to study human social networks. He has thus been able to compare the properties of protein interaction networks with those of other large systems such the internet or an ecosystem.
By comparing the networks of various cellular systems, he hopes to expose their vulnerabilities and also find out where the networks breakdown in the case of disease.
Thank you to Abigail Bird for her assistance in setting up the interview and for wiring up the podcast at the Dana-Farber Cancer Institute.
Part I - The Nuts and Bolts of Systems Biology
WARNING: The following episode is highly technical and classified as EXTREME BIOTECH, please proceed with caution.
We spoke with Dr. Vidal, and I have to say that he is doing some really cool geno/proteo/interact- omics-- endeavoring to transform molecular biology into true systems biology. While most of us are using a reductionist approach to molecular biology, one gene/protein function at a time, Dr. Vidal tackles entire genomes single-handedly (well almost). His eclectic methodologies are changing the way geneticists think about everything from comparative and developmental biology to the genetics of disease.
At the Dana-Farber Cancer Institute in Boston, Dr. Vidal and his team clone entire genomes and then engineer a model organism to express the genes in pairs. In doing so, they identify interactions among their encoded proteins. The result is a comprehensive protein interaction map - a bio-molecular "google earth" of sorts, by which scientists can visualize entire networks of proteins and assign function through association. Dr. Vidal begun this work on the nematode worm, and has now included the human cell to his cartographic expedition. Surprisingly, the human and worm genomes are not that dissimilar, each having approximately the same number of genes.
Now with the human genome completed, Dr. Vidal has begun making the human protein interaction map. In his first round, he has discovered 300 novel protein-protein interactions with 100 disease-related proteins. Some of these newly found interactions have the potential to be pharmacological targets.
While we mostly covered the nuts and bolts of the technologies he uses, next week in Dr. Vidal part II, we will focus on the concept of networks in systems biology, that is, how one can examine complex networks of genes/proteins rather than looking at genetics on a one gene, one function basis.
You can find out more about Dr. Vidal's work at the Vidal Lab
Thank you to Abigail Bird for her assistance in setting up the interview and for wiring up the podcast at the Dana-Farber Cancer Institute.
Great questions! From Wizard of Aus
What is a homolog?
A gene that is a homolog to another means that it shares a common ancestral DNA sequence. If you were to compare the DNA sequences, you would see regions were the sequence is identical. This could include genes that were duplicated within an organism or simply comparable genes between two different species.
What is a ortholog?
A gene that is an ortholog to another means that it is from a different species, and (1) it shares a common ancestral DNA sequence, and (2) the protein generated from the genetic code has retained its properties and function. You can verify this by taking a human homolog of a yeast gene, and introducing it into a yeast. If it restores a mutant yeast to behaving normally, you know that it is has retained it's function and would be considered an ortholog.
What is an enzyme?
An enzyme is a protein that acts like a chemical catalyst, that is it speeds up or facilitates a chemical reaction. An enzyme called glucosidase for example would break a chemical bond found in a sugar, or a protease woud cut a protein, a kinase adds a phosphate (PO4) to a protein etc... Enzymes are involved in metabolism, molecular signaling etc..
I hope this helps. It may require a couple reads through. When I first read about this stuff it didn't sink in right away.
Try the following:
(1) copy this DNA sequence (it's human):
1 ggcacgtgac ggtcgggccg cctccgcctc tctctttact gcggcgcggg gcaagatcat
61 ggaagggaag tggttgctgt gtatgttact ggtgcttgga actgctattg ttgaggctca
121 tgatggacat gatgatgatg tgattgatat tgaggatgac cttgacgatg tcattgaaga
181 ggtagaagac tcaaaaccag ataccactgc tcctccttca tctcccaagg ttacttacaa
241 agctccagtt ccaacagggg aagtatattt tgctgattct tttgacagag gaactctgtc
301 agggtggatt ttatccaaag ccaagaaaga cgataccgat gatgaaattg ccaaatatga
361 tggaaagtgg gaggtagagg aaatgaagga gtcaaagctt ccaggtgata aaggacttgt
421 gttgatgtct cgggccaagc atcatgccat ctctgctaaa ctgaacaagc ccttcctgtt
481 tgacaccaag cctctcattg ttcagtatga ggttaatttc caaaatggaa tagaatgtgg
541 tggtgcctat gtgaaactgc tttctaaaac accagaactc aacctggatc agttccatga
601 caagacccct tatacgatta tgtttggtcc agataaatgt ggagaggact ataaactgca
661 cttcatcttc cgacacaaaa accccaaaac gggtatctat gaagaaaaac atgctaagag
721 gccagatgca gatctgaaga cctattttac tgataagaaa acacatcttt acacactaat
781 cttgaatcca gataatagtt ttgaaatact ggttgaccaa tctgtggtga atagtggaaa
841 tctgctcaat gacatgactc ctcctgtaaa tccttcacgt gaaattgagg acccagaaga
901 ccggaagccc gaggattggg atgaaagacc aaaaatccca gatccagaag ctgtcaagcc
961 agatgactgg gatgaagatg cccctgctaa gattccagat gaagaggcca caaaacccga
(2) go to the national center for biotechnology information database
then click on (in the first box):
Nucleotide-nucleotide BLAST (blastn)
(3) Paste the sequence in the search box and click on BLAST.
(4) On the new page, click on Format
This allows you to compare the human gene to all the genes in the database. There will be mouse, rat, chicken versions... If the sequences are really close, they could be experimentally verified to see if they retain function, hence orthologs...
Dr. Leonard Guarente has identified the genes that could extent the human lifespan...
Will biotechnology allow us to live healthy and active lives well into our 100s? When the Novartis Professor of Biology at MIT says that it is not only possible, but a pill may be available within 10 years, it seems clear that we have entered new era of modern biotechnology.
Dr. Guarente started his work by studying aging in brewers yeast. In those experiments he identified a gene, called SIR2, that was responsible for dramatically extending the life span of yeast. It was soon found in other organisms such as round worms, fruit flies, and even mammals including humans for which there are 7 orthologs (or versions). The quest that has gone on since the pharaohs of Egypt, is now over, at least for all the models organisms tested to date! Are we next?
Would it be possible use this knowledge to delay the onset of age-related diseases such as diabetes and cancer? Dr. Guarente is working on the fundamental processes of aging in his lab, and the company he founded, Elexir Pharmaceuticals, is engineering the pharmacological solutions!
For more on Dr. Guarente’s work: the Guarente Lab
Also: Ageless Quest: One Scientists Search for Genes That Prolong Youth
Everyone big on biotech - it will never happen
Submitted by klynchk on 16 June, 2006 - 4:05pm.
Great podcast - really loved it - I want to know about this stuff. especially as some of the most important questions for society will come from this arena.
However I don't think Biotech is the next big thing in tech because the cost of entry to access the equipment is so phenomenal, whereas anyone can access a PC and create content I know you could say that about computers in 1976 but we always knew that they'd become mass market. What would I want a gene sequencer for in my house. Why and how would I breed fruit flies? on the other hand the day I saw a modem the size of a filing cabinet - I knew I would have one - just can't say the same for biotech.
You are right, and though the same thing goes for space exploration...
Submitted by Marc Pelletier on 17 June, 2006 - 12:00pm.
They are nonetheless REALLY cool. Generally it costs around 50 - 100k$/year to putter in biotech, whereas you can find an old pentium III at a tag sale, install linux and a ton of open source software, and create the next Skype. So you are definitely right on that...
Science is interesting in a different way. It continuously pushes the limitations of humankind back and gives us a better perspective on our existence: our place in the universe and how this universe works - sound preachy? Maybe, but think about what must have gone through James Watson's mind when he first saw the structure of DNA. He and Francis Crick, for a few hours, understood the human existence and life on earth better than anyone. This seems pretty cool to me. I want to be there when the frontier moves forward, and possibly take a few people along for the ride.
Now that I am done preaching, anyone can explore the human genome and download bioinformatic tools for free. The human genome is OPEN SOURCE!
Many genomes and some cool tools are available here:
Have fun data mining!