The LavaAmp is a portable PCR thermocycler that has the potential to become the default garage biology (home biology, bioDIY, DIYbio) tool once it hits the market. Think of Apple II for personal computing or MakerBot for 3D printing.
The 1st LavaAmp prototype was shipped this week from Biodesic to Gahaga Biosciences and the process is documented and engineering details uncovered in Rob Carlson’s post.
The people behind are mainly ex SciFoo Campers and open science advocates: Guido Nunez-Mujica, Joseph Jackson, Rob Carlson, Jim Hardy and a cool engineer Rik Wehbring.
Herein, we introduce an innovative thermocycling system that
harnesses natural convection phenomena to amplify DNA rapidly by the PCR in a greatly simplified format. A key element of this design is an architecture that allows the entire thermocycling process to be actuated pseudo-isothermally by simply maintaining a single heater at a constant temperature, thereby enabling a pocket-sized battery-powered device to be constructed at a cost of about US$10.
Realizing the potential of the device and thinking about how to build a digital thermocontroller for it with the Arduino I contacted Victor Ugaz this January and was informed that they only built the proof-of-the-concept devices testing them in the lab interested mainly in ‘understanding the physics of the thermally driven flow and its effect on the reaction’. But it was obvious to me that somebody will produce those devices for the market and make them affordable to people as it seemed to me as the familiar case of the low(est)-hanging-fruit.
So when Joseph Jackson mentioned to me his grandiose open science plans and the groups’ ‘super affordable pcr’ project I became instantly interested. As Rob Carlson writes:
The intended initial customers are hobbyists and schools. The price point for new LavaAmps should be well underneath the several thousand dollars charged for educational thermocyclers that use heater blocks powered by peltier chips.
Sage Bionetworks is a not-for-profit organization developing an open-access “pre-competitive” platform for networked and annotated models of human disease. It’s a huge and unparalleled bioinformatics enterprise: starting with an anonymous $5 million donation and soon making high throughput, large-scale human and mouse biological data (largely from Merck) available in the range that’s already in the public domain today. The co-founders are real big shots, Stephen Friend, a former successful Merck Executive and Eric Schadt, now a Chief Scientific Officer of Pacific Biosciences, who is “an industry leader in network biology with a number of high-profile publications over the past 5 years that have energized the systems biology community.”
For the last couple of months there was only minimal information available on the Sage website but now scientists interested can get the big picture in more details via a significant update.
The strong motivation behind is to build an open-access standard platform for human disease biology because
human disease biology has no common languages, no accessible communal repositories and no government, corporate or foundation investment in generating an inclusive resource….The experimental data underlying disease biology, like the genome itself, needs to be open access because the data is simply the beginning of the process….
Human disease biology is so complex, interconnected and expensive to research that the existing dominant business strategies of building and patenting unique models need to be replaced by a common standard. Like the internet, disease biology models will gain strength by their very nature as public platforms for interoperability and communication – this approach is at the very heart of that strength.
At the heart of the Sage model are the so called Global Coherent Datasets that will be for the first time available for scientists working all around the world. We’re talking about a real goldmine here for researchers:And if that doesn’t sound good enough for a start then the following Sage Datasets will be available in 1 to 2 years: Read the rest of this entry »
Nature’s Journal Club column is usually a good & always a short read providing exciting angles on scientific topics/papers from good researchers. Recently ‘neuroscientist’ Dave Featherstone argued for a broader approach to brain mapping by not restricting it only to the connectome between neurons. Neurons are making up less than 10% of the human brain while most brains cells are glia neglected by scientists making the wiring diagram of a ‘complete’ human brain.
For example, consider the recent study of adenosine and sleep led by Philip Haydon and Marcos Frank at the University of Pennsylvania in Philadelphia (M. M. Halassa et al. Neuron 61, 213–219; 2009). Adenosine binds to receptors on neurons, thereby regulating neuronal signalling. Interestingly, adenosine seems to represent ‘sleepiness’: it accumulates during wakefulness and dissipates during sleep. Where does it come from? It is generated from adenosine triphosphate (ATP), which is secreted by astrocytes — a major type of glia. Therefore, if we want to map the functional brain connections controlling sleep, we need to include glia and the extracellular space between glia and neurons. If we’re going to understand brain function by mapping the brain, we need to include most of the brain in our map.
I tried to draw an analogy between the situation in brain mapping and personal genomics on FriendFeed:
Update: it seems Dave Featherstone had something similar in mind as an analogy, he answered my email the following way:
Yeah, that’s a good analogy. The original version of my column said the connectome would be like if the human genome had only sequenced exons. But that sentence was cut for space considerations.
Surprise email from Conor McKechnie, GE Healthcare proving the aesthetics of science and the value of blogging:
A while (!) back you posted an inspiring piece linking to Harvard’s BioVisions inner life of the cell – it was 2006…It got me thinking that we could do something similarly inspiring with actual cellular images entered into our annual cellular analysis image competition. It took 2 years to make it happen, but finally: We have just posted a social media release highlighting the winners’ images being shown on the jumbotron in Times Square, with a short narrated film about the images and what they could mean for medical research, posted on YouTube:
Video interviews with the winners in Times Square on YouTube:
Short listed entries on a public site to inspire and encourage people to share in the beauty of science.
I hope you enjoy the links – and thanks for being the initial spark of inspiration.
After the Nature cover article Hugh Rienhoff and the story of My Daughter’s DNA is now covered by Wired magazine. I wrote about Hugh (a fellow SciFoo Camper) as an example of any future bioDIY effort in The conditions of a mass biotech DIY movement and now the Wired piece gives us more context and details concerning how things were actually done. This is really a story that cannot be overemphasized by simply telling it again and again.
By making inquiries with local surplus brokers, Rienhoff discovered he could buy a secondhand PCR machine for less than a MacBook. He ended up purchasing a full working model for just $750. Obtaining additional supplies, like the PCR reagents, for his experiment was tougher. Some chemical companies didn’t want to ship to a private address, so Rienhoff pretended his house was the headquarters of the fictional Institute for Future Study.
While Rienhoff could spring for his own PCR machine, a used gene sequencer (assuming he could find one) would cost around $100,000. So he found a university lab (which he declines to identify) that would sequence the genes he had amplified, for $3.50 per 50-microliter sample. In spring 2007, Rienhoff mailed in more than 200 samples.
Rienhoff compared Beatrice’s DNA with the information on Ensembl, looking for any base-pair variants that hadn’t been previously recorded on Ensembl. Read the rest of this entry »
Nature’s newest issue has a Quantitative genetics supplement with 3 free access pieces included out which I find this review the most interesting: Reverse engineering the genotype–phenotype map with natural genetic variation by Matthew V. Rockman. There’s a lot information to digest and many patterns to understand in this background field in order to approach the future of (personal) genetics/genomics.
forwarded, nonpersonal mail from Maya Kennard (you might get that email too):
Resource link/Story suggestion for your website:Title: VADLO – Biomedical Search Engine
Description: Vadlo is a search engine for the biology/biomedical scientists, educators, clinicians and reference librarians. References
Also check the Daily cartoons!
The idea is that we feed them with searches and links and they will grow big enough to give us more and more relevant searches and links. Magic concept: scalability, check the motivation behind the name choice:
Vadlo: (vud-lo) – Vadlo is a large fig tree characterized by aerial roots that eventually become accessory trunks. This allows it to grow horizontally to amazing proportions.
I find the 5 basic search categories amazing and after a short tinkering it can already throw out interesting sources:
From the about page:
Protocols category will let you search for methods, techniques, assays, procedures, reagent recipes, plasmid maps, etc. Online Tools Read the rest of this entry »
I only read 1 piece so far by Erika Check Hayden, who has the exclusive freedom at Nature to always pick the best stories and write on any of them, but being a heavy 23andMe user I was instantly reminded again on the program Promethease with which I can extend the interpretation of my data with an approximately 2 hour run.
According to two commercial gene-testing services — 23andMe and deCODEme — US Army medic Timothy Richard Gall of Fort Belvoir, Virginia, has a higher-than-average risk of basal cell carcinoma, type 2 diabetes and psoriasis. But much more enlightening than these results, which cost Gall more than $1,400, was a free online program called Promethease that he used to further analyse the data. By offering more in-depth information and interpreting of more of his genetic variants, Promethease “gives a much more realistic view of the usefulness of the information”, Gall says.Start-ups and services such as Promethease are now developing ways to improve the limited value of information provided by personal genomics companies for consumers and scientists alike.
Green fluorescent protein (GFP) is something really familiar for many biologists, now it will be familiar for the whole world for a period via the Chemistry Nobel Prize:
The remarkable brightly glowing green fluorescent protein, GFP, was first observed in the beautiful jellyfish, Aequorea victoria in 1962. Since then, this protein has become one of the most important tools used in contemporary bioscience. With the aid of GFP, researchers have developed ways to watch processes that were previously invisible, such as the development of nerve cells in the brain or how cancer cells spread.
The Institute for the Future‘s X2 project is all about tracing future trends in science and technology As the steward of the Biomedical Sciences and Biotechnology Group I collect signals in these fields on which some forecasts can be based later on. Here are some issues I found future sensitive enough recently:
It was already known that amongst the Google top people Sergey Brin is the one who is most interested in pushing biotechnology and the biomedical sciences: in his Stanford years he was interested in biology courses according to The Google Story, he married Anne Wojcicki (who graduted from biology at Yale), Google invested $4.4 million into 23andMe the pioneering personal genomics company co-founded by Anne, then Google invested into 23andMe competitor Navigenics too.
Now Sergey Brin added another, serious and personal reason to think that he is really, personally committed to the quick progress in the biomedical sciences: in his new blog – already a bit of an Internet history – called Too he disclosed that using the 23andMe personal genetics service he figured out something worrying about his and his family’s risk of Parkinson disease (his mother and her aunt are being already diagnosed with PD):
“I learned something very important to me — I carry the G2019S mutation and when my mother checked her account, she saw she carries it too. The exact implications of this are not entirely clear. Early studies tend to have small samples with various selection biases. Nonetheless it is clear that I have a markedly higher chance of developing Parkinson’s in my lifetime than the average person. In fact, it is somewhere between 20% to 80% depending on the study and how you measure.
The G2019S mutation is actually the rs34637584 SNP and lies in the gene LRRK2 encoding leucine-rich repeat kinase on chromosome 12. The mutation affects the first codon of the gene and is a guanine (G)-to- adenine (A) substitution resulting known as a missense and leads to a glycine – serine (hence the name) amino acid conversion in the protein product. Here is how the SNP position looks in the 23andMe browser using the sample family, the Mendels.
As the second operation of building my genetically well informed future yesterday (2 days after completing the order) I collected 2 ml of my saliva with the help of 23andMe’s Oragene DNA self-collection kit manufactured by DNA Genotek. First operation has been the sequencing of the D-loop of my mitochondrial DNA out of 5 ml of saliva in the lab at Tulane as a last control experiment, more on that later.
I’d be curious to know approximately how many people in Hungary or in Central Europe, or in all Europe have already used personalized genetics services like 23andMe or the Iceland based deCODE genetics’ genotyping services. As the whole industry is less than 1 year old (starting November 2007) there are not too many public stats available or at least I haven’t found any. With the recent (8th Sep) announcement of the modest $399 kit price reduced from $999 the pioneering personalized genetics service is now affordable for a lot more people, like me (compare it to the $600 iPhone early adopter fee, which I was unable not to buy). Read the rest of this entry »
BioBarCamp is due in circa 3 weeks and we have now 45 BioBarCampers signed up on the list of attendees and our host the Institute For The Future has the capacity for around 55 more campers, roughly for 100 people in general. We already have a very valuable mix: researchers, biologists (grad, postdoc, PI), coders-engineers-bioinformaticians, biotech entrepreneurs, doctors, science journalists.
Here is the list so far and that’s also a chance for you to decide whether you want to join and meet us there in Palo Alto on the 6th and 7th, August and share, ask and answer, be the donor and receptor of ideas from all around biogeekdom. I am continuously trying to collect some links on the campers on the BioBarCamp FriendFeed Room to make future Campers preconnected.
Finally Chris over at Ouroboros came up with the idea and the quick implementation of Hourglass, a blog carnival devoted to the biology of aging/biogerontology. For some reason I am not an explicit supporter of blog carnivals – many of my posts were chosen by carnival editors but I never hosted one -, but Hourglass will be the big exception in which I participate, submit posts and host it later. The reason: first it presents aging/biogerontology related posts, which fits my profile and second it was instigated by Chris Patil, whose work is a guarantee for keeping all this in the good direction. So if you want to read on the evolution of longevity and aging, calorie restricition, stem cells/tissue engineering/regenerative medicine, or on the association of long life and intelligence at once, Hourglass is for you.
The concept of decellularizing complex organs in cadavers and reseeding the remaining matrix structure with differentiated, stem or progenitor cells, growing in a bioreactor and transplanting back to the organism could turn out to be a real technological shortcut in the field of tissue engineering. It is not a brand new story on the web, but it is quite new in science and when I heard Doris Taylor at the Understanding Aging Conference talking on that….well I was really amazed.
Dr. Taylor not only showed the pictures of a complete decellularized rat heart matrix, but in fact they did it on a whole rat framework. So the obvious question is whether the technique could be extended to complete human cadavers (imagine the bone and the bone marrow situation) and if yes, when and how? I am sure if there were a useful clinical near term application of this type of tissue engineering, people would include that option too into their testaments.
And now a pop video on the topic and the abstract:
I argued many times here that biology based biotechnology is the next information technology but in order to do so, biotech should harness good IT patterns and mimic its massive computing practices to handle the enormous amount of constantly accumulating data. Often this trend could be summarized in a simple way: keep your eye on Google and conduct thought experiments in advance in which science is done in a Googleplex like environment in terms of the computing & financial resources and algorithm heavy engineering culture. Use Python and learn cluster computing and MapReduce. With the expected launch of the massive scientific dataset hosting Google service – nicknamed Palimpsest – this year finally a direct interface between scientists and Googlers emerges and hopefully opens up possibilities for scientists to cooperate with Google. (Remember my joke on Google BioLabs back in 2006)? I get emails from biologists, bioinformaticians asking me how to be hired by Google ever since then. As I tweeted yesterday: I growingly have the impression that “being ambitious” today = ‘worked, is currently working, is going to work at/for Google’ Taking Google’s inter-industrial power into consideration I see a real chance that some day the “Google of Biotechnology” title goes not to a startup yet to be emerged, not to Genentech or to 23andMe but……to Google itself. No kidding here. Fortunately Google’s model is “to build a killer app then monetize it later” says Andy Rubin, the man behind Google’s Android mobile software in the July issue of Wired so scientists working for the big G probably won’t have to worry about turning their scientific killer app into an instant cash machine.
And now in the very issue of Wired magazine (not online yet ) there is an exciting cover story on the same pattern I talked about concerning the life sciences but in the broader context of every kind of science with the provocative, Fukuyama-like title The End of Science. There is a witty and short essay from editor-in-chief Chris Anderson entitled The End of Theory followed by examples of the ‘new science’ like the The Large Hadron Collider expected to generate 10 petabytes if data/second, The Sloan Digital Sky Survey heaven catalog maker accumulating 25 terrabytes of data so far, the skeleton scanning project of Sharmila Majumdar and the Many Eyes project “where users can share their own dynamic, interactive representations of big data”.
For many people around the globe, Chris Anderson is a freeconomist & the author of a popular airport book but fewer people are aware that he was actually trained as a (quantum) physicist and even worked at Los Alamos Read the rest of this entry »
Even tech people in Silicon Valley need to join their powerful forces and sources when it is about aging related neurodegenerative diseases and help research and the clinic.
It’s official: The California Department of Public Health wants practicing physicians (many of them prehistorically, sorry, traditionally trained) to be the patres familias in issues between personal genetic test takers and direct-to-consumer personal genetic testing start-ups while declining the test takers’ right to get familiar with their own genetic makeup and risks by their own. Calif. cracks down on 13 genetic testing startups
California health regulators have demanded that 13 direct-to-consumer genetic testing startups halt sales in the state until they prove they meet state standards. All the companies have two weeks to demonstrate to regulators that their laboratories are certified by the state and federal governments, said department spokeswoman Lea Brooks. The startups also must show the tests they are selling California residents have been ordered by a doctor as required by state law.
The “Understanding Aging: Biomedical and Bioengineering Approaches”conference will be held from June 27-29, 2008 at UCLA organized by Aubrey de Grey, Irina Conboy and Amy Wagers. I like to call it UndertsEnding Aging in myself and I am excited to go to LA and meet new people also people from SENS3.
Yesterday I created a FriendFeed room for the conference as it seems to be a perfect place of live microblogging the conference, sharing any kind of links, videos, comments, feeds and feedbacks. Working on aging and the postponement of it (you can bravely say life extension) is always a pioneering work so it’s time to use pioneering web apps for that purpose, just like FriendFeed.
Aubrey de Grey, Kevin Perrott and Kevin Dewalt have already joined the room. What about you? See you on FriendFeed, see you on LA!
I would like to provide you with a copy of the press release to be distributed via press release distribution sites on Wednesday. We will also put it on our site within a few hours after this email so you can confirm its authenticity. Please help us distribute this press release.
The Biogerontology Research Foundation, which has been started with the help of worlds’ most prominent scientists and businessmen received the charitable status from the Charity Commission for England and Wales.
The fact, which is not mentioned in the press release is that the chief scientific officer of the foundation is Dr. Michael Rose of UCI, who is famous for extending life of fruit flies threefold.Read the rest of this entry »
Also a good presentation by Linda Avey, other co-founder, for instance on data privacy and service security:“We take the security of our customers’ data to the highest degree…you guys (Googlers) are very much of the same mind..One of our leading engineers is probably the most paranoid man we’ve ever meet and he is the perfect guy for that.
Here are my screenshots on the genetic puzzle on the Google triumvirate presented by Anne Wojcicki:
When I wrote about BioBarCamp for the first time, it was just an idea to organize an unconference for biogeeks, people interested in life scientists around SciFoo Camp time.
Sometimes in looking forward it’s good to look back. In cardiac regenerative medicine, probably the only clear success to date is heart transplantation. From the initial grant that Norman Shumway received in 1958 [to study the possibility of heart transplantation] it took more than two decades before the procedure became routine.
Shumway was a careful, thoughtful man. He not only didn’t do the first heart transplant; he didn’t do the second. He was slowed down in the United States because of the regulatory barriers and ethical concerns. Christiaan Barnard, on the other hand, went back to South Africa and decided to just go for it. Sounds familiar?
We realized very quickly that this was not working, that the science was not there. In 1968, a year after his first attempt, Barnard gave up on the procedure and considered it a failure. Everyone gave up, except Shumway. He went back to the lab and spent the next ten years figuring it out. He realized that the issue was rejection.Read the rest of this entry »
As of this moment the population of The Life Scientists Room on FriendFeed is 73. See the BioGang in motion and get an initial statistics on the distribution of wet lab/dry lab, academic/industrial people there. Here are the first 8 answerers out of the 16 so far.
“This paper outlines prospects for applying the emerging techniques of synthetic biology to the field of anatomy, with the aim of programming cells to organize themselves into specific, novel arrangements, structures and tissues. There are two main reasons why developing this hybrid discipline – synthetic morphology – would be useful. The first is that having a way to engineer self-constructing assemblies of cells would provide a powerful means of tissue engineering for clinical use in surgery and regenerative medicine. The second is that construction of simple novel systems according to theories of morphogenesis gained from study of real embryos will provide a means of testing those theories rigorously, something that is very difficult to do by manipulation of complex embryos. This paper sets out the engineering requirements for synthetic morphology, which include the development of a library of sensor modules, regulatory modules and effector modules that can be connected functionally within cells. A substantial number of sensor and regulatory modules already exist and this paper argues that some potential effector modules have already been identified. The necessary library may therefore be within reach. The paper ends by suggesting a set of challenges, ranging from simple to complex, the achievement of which would provide valuable proofs of concept.”
Finally I started to digest all the articles (usually on the streetcar on my way to work and home) from the recent Nature Insight: Regenerative Medicine and I try to pick up some stories for you (& interesting enough for me) from that, in case you are not lucky enough to have an available copy.
For clinicians, the lack of gold standard embryonic stem cell lines with the measurably same regeneration potential will be a huge technological problem later while this variability is an interesting basic science problem today.
A central challenge to the development of human stem-cell-based models of disease lies in the need to isolate and expand rare cell populations reproducibly and then to fully differentiate enough of the cells of interest. In this regard, one of the main obstacles to establishing human ES-cell-based models is that ES cell lines vary. All lines do not have the same potential to differentiate into cells of a particular lineage, most probably as a result of inherent epigenetic, genetic and developmental differences at the time of their isolation. For example, a study of 17 independent human ES cell lines showed that 7 of these lines had little or no capacity to enter the cardiovascular lineage, and the level of cardiovascular markers expressed by 2 of the 17 cell lines was an order of magnitude or more higher than that of these 7 lines. Similar variability between human ES cell lines was observed for entry to the pancreatic lineage, and cell lines that were optimal for generating cells of endodermal lineages were extremely poor for generating mesodermal lineage cells in many cases. Thus, new human ES cell lines that are optimal for generating specific lineages of interest need to be produced. In addition, iPS cell lines might be similarly variable.Read the rest of this entry »
Desktop background images are important parts of people’s everyday lives in terms of unintended staring time. Usually they are picked up for the eyes (sg spectacular & cool and/or sexy) and hearts (family members), but why not use them for information uptake and learning? So I’d like to ask: What’s your current science related desktop image, if there’s any and how can you utilize it? Here is my current desktop image with the source;
Bonnet et al.:
A Mitochondria-K+ Channel Axis Is Suppressed in Cancer and Its Normalization Promotes Apoptosis and Inhibits Cancer Growth Cancer Cell Volume 11, Issue 1, January 2007, Pages 37-51
Figure 1. A Reversible Metabolic-Electrical Remodeling in Cancer Contributes to Resistance to Apoptosis and Reveals Several Potential Therapeutic Targets
Nature Biotechnology is the (peer review) journal for me: it’s geeky, fresh and it takes into account more than just one point-of-view, that of the scientist-academist’s: technology & business are hand in hands also. (Recommending Nat Biotech makes a niche sense here while recommending Nature, which is actually the only science journal I’m reading issue by issue is hm… too obvious)
But Nature Biotech goes as far as citing even a non peer review journal – I am also prettyfamiliar with – called Wired. So my puzzle is /please use your contextual knowledge first & just then your typing skills while thinking of an answer/: which Wired article is cited in a March Nature Biotech News and Views article (very good, by the way) named Synthetic genomes brought closer to life by Robert A Holt amongst strict science articles. Don’t think too high, it’s rather a reflection.
David Secko writes: “Today, it is thought that one third of the proteins present in a typical mammalian cell are covalently bound to phosphate (i.e. they are phosphorylated at one time or another)”
Well I haven’t checked what kind of measurement the above 1/3 estimation is based on but if true it is no wonder that phosphorylation is the almost constant subject of biological research. But if it is not true, then what’s the reason of the stardom?
It seems that my favorite ever unconference, the SciFooCamp will be aroundunconferenced by a BioBarCamp this year. The whole idea of the BioBarCamp is based upon the SciFoo Camp, so it is by no means a competitive but a complimentary event.
From the BarCamp wiki: “The BioBarCamp is an idea (fed by the tweets of the BioTwitterer community) to organize a life sciences – biotechnology – personalized genomics & medicine – bioinformatics unconference at the Bay Area around the 3rd SciFoo Camp time, which is 8-10th August. The SciFooCamp generates a lot of enthusiasm & activity but not just for those who are invited (only 200). On the other hand, it would be nice to organize a bio-related BarCamp, just like the Cambridge BarCamb, in which the bio-related SciFoo Campers and all the other biogeeks could gather together.”
The main activity is happening right now at the public BioBarCamp Google Group. If interested please join there or just follow the discussions. We are right now in the process of finding a proper venue and sponsors and any help would be most welcome. Right now 6 or 7 August seems to be the consensus day and we have a very generous offer from The Institute for the Future via Alex Soojung-Kim Pang in Palo Alto (no response from 23andMe so far, see below).
It’s against a classic Twitter story, just like this before. You can reconstruct the whole conversation with Twitter Search Engine Tweet Scan by searching for terms SciFoo, BioBarCamp, SciBarCamp but here are my selected tweets:
Scene One, 04/10/08 How the idea was born on that day in reverse chronological order:
Scene Two 04/22/08 How the biospecificity and name was born alongside with a possible venue idea: Read the rest of this entry »
In order to have the slightest change to design a robust, systemic life extension technology, we need to accumulate every systemic macromolecular, cellular, tissue- and organ level data of the normal, physiological human body, connect the trillions of nodes with scalable software algorithms and suck out the draft of the proper sequence of consecutive treatment/regeneration steps later. Fortunately not only life extension technology needs systems biology projects (this is not enough for getting grants), but more importantly the effective design of new drug targets and the discovery of disease biomarkers are clearly crying for the systemic level. The urgent diagnostic and therapeutic demands are sufficient to launch international, many-lab projects.
Finally a complete ‘Human Proteome Project’ is in the pipeline (illustration via BioMed Search). It aims the tissue-level complete knowledge of the human proteome revealing “which proteins are present in each tissue, where in the cell each of those proteins is located and which other proteins each is interacting with”. Keep in mind also that around 21’000 human genes encode 1 million different proteins and that the effort cannot localize exactly which cell types in a given tissue is producing which protein.According to Nature’s Helen Pearson: Biologists initiate plan to map human proteome
“Those involved in the draft plan say that a human proteome project is now feasible partly because estimates of the number of protein-coding genes have shrunk. It was once thought that there might be around 50,000 or 100,000, but now, just 21,000 or so are thought to exist, making the scale of human proteomics more manageable. And the group plans to focus on only a single protein produced from each gene, rather than its many forms.
The plan is to tackle this with three different experimental approaches. One would use mass spectrometry to identify proteins and their quantities in tissue samples; another would generate antibodies to each protein and use these to show its location in tissues and cells; and the third would systematically identify, for each protein, which others it interacts with in protein complexes. The project would also involve a massive bioinformatics effort to ensure that the data could be pooled and accessed, and the production of shared reagents.”
The idea is to analyze and list all the proteins manufactured by chromosome 21 within 3 years as a pilot study and then finish the whole project within 10 years. Chromosome 21 is the smallest child in the family and likely contains between 200 and 400 genes, so the pilot study can yield us a couple hundreds proteins. Another powerful idea (actually I prefer this) is to start with the human mitochondrial proteome which is around 1000-1500 proteins as far as I know, that is at least 3 times as many as encoded by chromosome 21.Read the rest of this entry »
In the live thesis building blogxperiment I edit (digest, compile, write, rewrite, delete) my ongoing doctoral thesis in blog posts and put the parts together on thesis live. The title: The physiologic role of stem cells in tissues with different regenerative potential.
1.2. Tissues, organs with different turnover and regenerative potential
/bioenergetics data missing/
Liver
During organogenesis the hepatic endoderm epithelium invades the surrounding mesenchyme to form the liver bud and continued epithelial/mesenchymal interactions stimulate cell proliferation and morphogenesis. Consequently, the liver is largely of endodermal origin – including cells with a mesodermal origin and – and contains many different cell types: two epithelial liver cell types, the hepatocytes and bile duct cells, stellate cells (formerly called Ito cells), Kupffer cells, vascular endothelium, fibroblasts, and leukocytes (Desmet 1994). Hepatocytes are the main funtional liver cells accounting for ~70% of the cells in the liver and form the bulk of the liver weight (90%), yet only ~60% of total liver DNA is hepatocyte-derived (many of them with 2n, 4n, 8n DNA content). An adult human liver contains about 80 x10(9), hepatocytes. Hepatocytes are in a quiescent state and the turnover rate is low, 1-2 times/year[]. The remarkable regenerative potential of liver is well-known, in humans the liver almost completely regenerates in about 1 month after two-thirds (up to 75%) partial hepatectomy and this process can occur repeatedly in contrast to most other parenchymal organs, such as kidney or pancreas. In the literature the term liver or hepatic stem cells is used for precursors of the hepatocytes and the bile duct epithelial cells. On the other hand liver stem/progenitor cells can be define in different ways.Read the rest of this entry »
In the live thesis building blogxperiment I edit (digest, compile, write, rewrite, delete) my ongoing doctoral thesis in blog posts and put the parts together on thesis live. The title: The physiologic role of stem cells in tissues with different regenerative potential.
1.1 Stem cells and regenerative medicine
The concept of the stem cell niche was first proposed theoretically by Schofield exactly 30 years ago in the context of hematopoietic stem cells: “a hypothesis is proposed in which the stem cell is seen in association with other cells which determine its behaviour. It becomes essentially a fixed tissue cell. Its maturation is prevented and, as a result, its continued proliferation as a stem cell is assured. Its progeny, unless they can occupy a similar stem cell ‘niche’, are first generation colony-forming cells, which proliferate and mature to acquire a high probability of differentiation, i.e., they have an age-structure.”
Niches are restricted and specialized tissue microenvironments that integrate local and systemic signals for the regulation and maintenance for resident stem cells. The elements of the stem cell niche include the constraints of the architectural space, cellular components like stromal supporting and descendent/progenitor cells and acellular elements, like soluble and membrane bound molecules, paracrine and endocrine signals from local or distant sources and neural input [Figure by Jonas].
In the live thesis building blogxperiment I edit (digest, compile, write, rewrite, delete) my ongoing doctoral thesis in blog posts and put the parts together on thesis live. The title: The physiologic role of stem cells in tissues with different regenerative potential.
1.1 Stem cells and regenerative medicine: basic concepts
/turnover: cellular turnover/
The concept of biological turnover (rate) can be interpreted on many levels: molecules, molecular pathways (signaling), organelles, cells, tissues, organs. The turnover rate by which a biological entity is replaced can be quantified by measuring its half-life. /In abstract form “the half-life of a quantity whose value decreases with time is the interval required for the quantity to decay to half of its initial value” (Wikipedia) I have to check whether it is problematic to explicitly use a Wikipedia entry – I am sure it is used implicitly – in a PhD thesis/ The concept of half-life refers to the time required for an initial quantity of entity E to decay half of its initial value. According to Caplan [reference]: “Every cell in the body has a specific half-life; every cell comes to maturation and will, predictably, drop dead in due course.” For instance erythrocytes have half-lives of 60-90 days and the turnover rate of hepatocytes is 1-2 times/year. On Figure 1 from Caplan the lineage development of a differentiated cell and its replacement cell is delineated. The relative position of these two curves to one another defines growth, steady-state, or atrophy depending on when the first cell dies and when its replacement, the second cell, comes online. /I am not sure here how to solve the problem of legends in the case of figures coming from the literature but I figure it out, here is/
In the live thesis building blogxperiment I edit (digest, compile, write, rewrite, delete) my ongoing doctoral thesis in blog posts and put the parts together on thesis live. The title: The physiologic role of stem cells in tissues with different regenerative potential.
When producing a text, a post my building strategy is not linear, but heavily non-linear (I wouldn’t say it’s circular): I’d like to jump to the part of the story where there is something instantly to write/edit; be it the beginning, middle or end. In case of scientific articles frequently the first part to be build are figures/methods, which forms the bulk, the middle of the story after introduction, before discussion.
1.2. Tissues, organs with different turnover and regenerative potential
In order to discuss the different adult tissues in a unified manner, from a systemic point of view, I use the following tissue/stem cell introduction scheme where data are available: development of particular tissue, number of cell types, bioenergetics (high/intermediate/low energy demand), turnover (high/intermediate/low), regenerative potential (high/intermediate/low), resident stem cells, niche, markers, cell sources from other tissues that can contribute to the particular tissue during normal turnover or chronic/acute injury.
In the 2007 proof-of-concept paper, entitled A Pocket-Sized Convective PCR Thermocycler, authors Nitin Agrawal, Yassin A. Hassan, and Victor M. Ugaz wrote:
