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?

I got one of my smartest comment to my Human proteome project: 21000 genes/1 protein, 10 years, $1 billion? from a scientist at the University if Rochester that could suggest an answer:

“Another example - we study protein phosphorylation and we think it’s important. Why? Because we can! We have methods and tools to measure it, but all along we have absolutely no evidence that phosphorylation is any more important than the hundred of other protein modifications that we know exist. There could be upwards of 1000 PTMs on every single protein, and we have the technology to accurately study about 5 of these.”

Meet 2K, the 2,000 Year Old Programmer from the Bronx and Auto-ID in The MarkMagic Chronicles.

“That’s the problem these days,” 2K says. “Nobody wants to do work hard. Everybody wants easy. In my days, we knew what heavy lifting was. I had to carry rocks to my cave in the office. We carried rocks to write on. We wrote our code with a hammer and a chisel. That’s not software kid. That’s hardware.”

Says Alex Woodie:

The series, which gains inspiration from Apple’s popular “Mac versus PC” series and the old “2,000 Year Old Man” skit by Mel Brooks and Carl Reiner, pits 2K as the force of legacy against Auto-ID’s power of moder. 2K, the highly endearing, yet vertically challenged funny-man, who may resemble some (as yet un-mummified) RPG or COBOL coders in your shop.

You can also get a quick intro to industrial RFID tagging/printing:

The 2006 Nature Insight: Stem Cells edited by Nature Report Stem Cells editor Natalie DeWitt is still a basic reading for me. The newest Nature is accompanied by a similar supplement called Nature Insight: Regenerative Medicine

Just a simple filtering & highlighting & regurgitating for you based on Andy Oram’s post apropos of the opening of a larger Cambridge, Massachusetts Google office : Why open source developers can be more productive, and other tales from a Google open house

Along the lines of self-motivated employees, I asked a manager whether most of their new products came from the individual employees or from management. He expressed the conviction that most innovation in most companies comes from individual employees. Where management can help is in finding effective places to fit new features into the organization and product line.

Google found that releasing too many products prevented the public from learning about them and adopting them. Adding a feature to an existing product such as Gmail or Blogger could mean that millions of people adopt it, whereas releasing it as a stand-along product might limit adoption to a few thousand.

The question for me is always how these experiences can be compared and applied to the biotech industry, in this case I am curious how biotechnological innovation is going in the profit sector outside academia. So if you are working at a biotech startup or at a big pharma please share us your opinion (anonymously if you like) in the comments on the nature of innovation at your company!

Say Hello to my new 2.4 GHz Intel Core 2 Duo, 4GB RAM, Mac OS X 10.5.2 MacBook right from the Fifth Avenue Apple Store, New York City! We are back in New Orleans waiting for the swarm of the formosan termites.

Let me recall some Manhattan moments with the help of quick iPhone photos.

F. Murray Abraham is one of my favorite actors, the Coen Brothers are one of my favorite movie makers. So we enjoyed ‘Almost an evening‘ the first ever play of Ethan Coen (half of the Coens) featuring Abraham as god amongst others in Bleecker Street Theatre, Off-Broadway. (The play itself probably won’t be an evergreen.) /picture at the top right corner via Flickr

a very geek Warhammer game player at the end of Washington Square Park in the Village

Times Square from the 29th floor of the Ernst & Young Building

dead Barbie at Central Park

Malcolm Gladwell has a nice, but a bit Microsoft heavy essay on scientific/technological multiples, ie. the phenomenon of simultaneous discovery in New Yorker: In the Air

Gladwell argues that it is always misleading to apply the paradigm of artistic invention to scientific/technological invention and he is probably right.

Two sections just for your appetite:

“This phenomenon of simultaneous discovery—what science historians call “multiples”—turns out to be extremely common. One of the first comprehensive lists of multiples was put together by William Ogburn and Dorothy Thomas, in 1922, and they found a hundred and forty-eight major scientific discoveries that fit the multiple pattern. Newton and Leibniz both discovered calculus. Charles Darwin and Alfred Russel Wallace both discovered evolution. Three mathematicians “invented” decimal fractions. Oxygen was discovered by Joseph Priestley, in Wiltshire, in 1774, and by Carl Wilhelm Scheele, in Uppsala, a year earlier. Color photography was invented at the same time by Charles Cros and by Louis Ducos du Hauron, in France. Logarithms were invented by John Napier and Henry Briggs in Britain, and by Joost Bürgi in Switzerland.”

Let’s meet Stiegler’s law:

“The statistician Stephen Stigler once wrote an elegant essay about the futility of the practice of eponymy in science—that is, the practice of naming a scientific discovery after its inventor. That’s another idea inappropriately borrowed from the cultural realm. As Stigler pointed out, “It can be found that Laplace employed Fourier Transforms in print before Fourier published on the topic, that Lagrange presented Laplace Transforms before Laplace began his scientific career, that Poisson published the Cauchy distribution in 1824, twenty-nine years before Cauchy touched on it in an incidental manner, and that Bienaymé stated and proved the Chebychev Inequality a decade before and in greater generality than Chebychev’s first work on the topic.” For that matter, the Pythagorean theorem was known before Pythagoras; Gaussian distributions were not discovered by Gauss. The examples were so legion that Stigler declared the existence of Stigler’s Law: “No scientific discovery is named after its original discoverer.” There are just too many people with an equal shot at those ideas floating out there in the ether. We think we’re pinning medals on heroes. In fact, we’re pinning tails on donkeys.”

Anna and me are visiting New York City from 8th to 11th, Sunday this week. We are eager to meet geeky figures particularly as our current location, New Orleans is not really a heaven for tech-savvy people. If interested to meet with us, drop me a line: [attilacsordas][at][gmail.com]

With the public launch of the X2 project, Alex Soojung-Kim Pang realized one of his dreams. Alex is the research director of The Institute for the Future (IFTF), an independent nonprofit research group headquartered in Palo Alto, Silicon Valley. He writes:

The project is called X2, and its aim is to forecast the future of science, technology and innovation. The name may sound like science fiction, but it’s actually an historical allusion. In my previous life as an academic historian, I studied the X Club, a group of Victorian scientists who were very interested in the future of British science. The Club formed when its members were still young, ambitious outsiders, fighting to establish their reputations in a world in which social connections and privilege mattered more than scientific achievement; by the time they retired, its nine members were among the leaders of British science.

That said, dear ‘still young, ambitious outsiders’ you can now sign up for the project and join the groups you’re interested in. I suggest you starting with Quick Start. Disclaimer: I am the so called “steward” of the embryonic group Biomedical Sciences and Biotechnology. As my job description says: …people who can provide a basic supply of high-quality signals and forecasts, and work with us to encourage others to contribute. Currently we’re calling these people “stewards. Signals are post-like entities: each signal is a few hundred words, plus links to exemplary online resources and tags, covering the most exciting, strange-but-potentially-revolutionary, or just plain important developments in the respective fields. Forecasts are intended to speak more explicitly to the future than signals, and explain how the trends they discuss might play out over time. Formal descriptions of signals, hypotheses, forecasts are here. Also you can be involved in prediction market game.

I became involved in the project in November, 2007 and contributed with some signals that later turned out to be forecasts. The designer of the site is Mike Love and Matt Daniels is the research manager.

The official description of the X2 project:

Today, science is entering another period of accelerated change, thanks to the growth of the Internet and dawn of pervasive computing; the explosive growth of new sciences like genetic engineering, nanotechnology, biotechnology, and simulation; the rise of new scientific powers in the developing world, the revival of amateur scientists, and the growth of citizen science movements in the United States and Europe; the growth of new institutions supporting scientific research and innovation, and changes in the structure and funding of universities, government, and corporate R&D labs. Science in 2025 and 2050 is going to look very different than it does today.

To map and make sense of all these changes, the Institute for the Future (IFTF) launched the X2 Project in late 2007. The purpose of X2 is to identify future disruptions, opportunities, and competitive landscapes related to the content and dynamics of global science and technology innovation; to develop a new platform for understanding global innovation trends; and to present this information to policy- and decision-makers, as well as the general public, in a useful form. The project conducts its research online, through an innovative experiment in open forecasting; in workshops with young scientists and engineers around the world; and in online games.

X2 is overseen by an ad hoc committee sponsored by the U.S. National Academies (comprised of the National Academy of Science, National Academy of Engineering, Institute of Medicine, and National Research Council), and received its initial funding from the U.S. Department of Defense.

It seems that my favorite ever unconference, the SciFoo Camp 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:

Scene Three 04/23/08 an instant and crucial help from Eva Amsen of Easternblot who happens to be one of the organizers of the Toronto SciBarCamp and also a Twitter user. Eva simply passed on the BioBarCamp info to her fellow SciBarCamp organizers Jamie McQuay and Jen Dodd. Eva’s tweet:

The 3rd Science Foo Camp, organized by Nature, O’Reilly Media, and Google will be held on August 8-10 and hosted at the Googleplex in Mountain View, CA.

From the mail: “Now in its third year, Sci Foo is already achieving cult status among those with a passion for science and technology. The Economist said that it “capture[s] the essence of innovation”; in a photo essay for Edge, George Dyson wrote of the “the impossible choice” when deciding which sessions to attend; another attendee described it simply as “The best gathering ever. Period.”

Also check the strongly related BioBarCamp idea.

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.

“Steven Carr, director of proteomics at the Broad Institute in Cambridge, Massachusetts, says there is likely to be broad support for a large-scale proteomics effort, but much debate about how best to do it. Rather than analyse the proteome of one chromosome, he says it may be better to tackle the proteome of mitochondria or the cell membrane because it would reveal more about biology and diseases related to those structures. “It’s time to think about something in a systematic fashion — whether this is the project is a different question,” he says.”

Chowder:

“Skull is in the game zone, right now. And you don’t want to mess with him when he is in the game zone. He once played for 4 days straight on 1 quarter, a gallon of chocolate milk and an adult diaper.”

Wow, I guess it’s time for me to move into the stock market business! Here’s the story via David Bradley’s tweet: Julie Kent, Search Engine Journal, April 21st, 2008: Google Wants to Index Genetic Information, Invests in Second DNA Start-Up

In 2007, Google made headlines when they invested $4.4 million in 23andMe, a genetic screening start-up company began by Anne Wojcicki, the wife of Google co-founder Sergey Brin, and a business partner. But if you thought that was Google’s only interest in genetics and DNA, you’re wrong. Google has also been investing in a second DNA start-up called Navigenics, which for $2,500 and a small bit of saliva will provide you with genetic test results delivered securely online containing information about the likelihood for 18 medical conditions.

What’s really funny here is that I predicted this investment last Friday, on the 18th, on Twitter. The original idea was Aaron Swartz’s Google thought experiment: Imagine you were suddenly put in charge of Google. What would you spend your time doing? I came up with this answer (picking Navigenics because of ther profile and location) on behalf of Sergey Brin:

The whole tweetstream:

Update after a little digging: This BusinessWeek article seems to be the original “breaking news” source: Google Wants to Index Your DNA, Too/it was online at April 18, 2008, 9:33PM EST while my tweet is dated to 02:54 PM April 18, 2008 /

Clive Thompson - undoubtedly a good journalist - has a piece, entitled Information Overlord in May Wired issue (not online yet, but already problematic) on his experience with semantic Web app Twine. Clive also formulates a provocative though about the value of information modulated social connections.

“But the truth is, sometimes social connections are less useful than semantic ones.
I’ve experienced this myself. My Facebook page attracts my friends, with whom I share social bonds. Meanwhile, my science blog attracts complete strangers, with whom I share a common interest in a topic - like a scientific study I’ve blogged about. It’s a semantic relationship, based on shared meaning. So those strangers tend to tell me things - and point me to links - that are more useful than the social stuff on my Facebook page. Information trumps friendship”

I am not sure whether the distinction behind: emotional, social friends vs rational, information only semantic cooperators is valid. I think of my good commenters as digital friends and many of my Facebook “friends” as not friends, just simple connections.

Twitter effects blogging habits in many ways (see the term microblogging) and it is frequently the premier source of fresh web information. The number of biology and science related Twitter users are steadily growing, so today I created the @biotecher account in order to find every biotech, biology, medicine, bioinformatics related twitterers at one place and follow them. That is a guide for newly registered Twitterers who want to find their professional community on Twitter too.
How does it work: at this point, manually, everyone who follows @biotecher will be reciprocally followed by @biotecher and the account info will be shared in order to expand the biotwitter bubble.

Update: A person that uses Twitter is a Twitterer rather than a Twitter.

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. The cells which give rise to regeneration after partial hepatectomy and in other liver injuries are differentiated hepatocytes with a virtually unlimited differentiation potential. This type of endogenous liver regeneration is progenitor independent. Transplanted hepatocytes also have the ability to repopulate damaged, injured recipient livers [Rhim et al 1994.] but the hepatocytes do not significantly repopulate normal adult liver following transplantation. Although unique liver stem cell markers are not currently available, “oval cells” are the best candidates for non-hepatocyte, progenitor-dependent liver regeneration. These cells have a high nuclear/cytoplasmic ratio, termed oval cells due to the initial morphology and their parent cells probably reside in the canal of Hering. Oval cells express markers of both bile duct epithelium (CK-7, CK19, OV-6) and hepatocytes (albumin, alpha-fetoprotein) and are bipotential; have the ability to differentiate into both of the major liver cell types (Sirica et al. 1990; Sirica 1995). Oval cells also express also express hematopoietic stem cell (HSC) genes (c-kit, CD34, Sca-1 and Thy-1) however the idea that hematopoietic stem cells in the bone marrow are the ancestors of oval cells seems improbable and several recent studies in mice and rats have shown that transdifferentiation of HCS into “oval cells” is a very rare event probably without physiological significance [Thorgeirsson S, Grisham J 2006]. Oval cells are facultative liver stem cells that is in case of specific chronic injuries, caused by chemicals such as DL-ethionine, galactosamine, and azo dyes they regenerate the liver in murine models.

Literature:

Thorgeirsson S,Grisham J. (2006) Hematopoietic cells as liver epithelial stem cells: a critical review of all the evidence, Hepatology 43 2–11.
http://www.cincinnatichildrens.org/research/div/dev-biology/fac-labs/zorn-lab/liver-dev.htm
Grompe M, Finegold MJ (2001) Liver Stem Cells Stem Cell Biology 455-497 Cold Spring Harbor Laboratory Press
Oertel M, Shafritz DA. Stem cells, cell transplantation and liver repopulation Biochim Biophys Acta. 2008 Feb;1782(2):61-74.
Rhim JA, Sandgren EP, Degen JL, Palmiter RD, Brinster RL. (1994) Replacement of diseased mouse liver by hepatic cell transplantation. Science. 263(5150):1149-52.

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].

Niches are dynamic entities, could be redistributed and ideally “a candidate niche should be transiently depleted of its full complement of stem cells and then shown to take up and maintain a newly introduced stem cell” [Morrison, Spradling, 2008, thanks for Ouroboros for picking this review]
Jones DL, Wagers AJ. (2007) No place like home: anatomy and function of the stem cell niche. Nat Rev Mol Cell Biol. 2008 Jan;9(1):11-21. Review.
Morrison SJ, Spradling AC. (200 Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell;132(4):598-611.

With TweetClouds (scripting: John Krutsch design: Jared Stein) people can generate the Tweet Cloud of a Twitter user. In case of bloggers/Twitters it is an interesting question whether there are any strong differences between the category cloud/Tweet Cloud of the same person suggesting patterns in web behavior. I’ve just generated mine. One obvious difference is that with TweetClouds including replies to other Twitters (there is an option to suppress @replies, but why would you?) there is also a social/networking component (check the names after @) instantly visible on the generated cloud.

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
In the adult kidney the nephrons (approximately 500 000 nephronic units/kidney) develop from the metanephric mesoderm/mesenchyme while the collecting ducts are coming from the ureteric bud. The kidney is a complex structure with at least 26 different cell types. The renal function is particularly age-dependent (loss of functional renal mass up to 25%). The kidney is an active tissue with high energy demand and contains a lot of mitochondria (especially in the proximal tubules). On the other hand, while the turnover rate is low, there is a robust although limited regenerative response to acute kidney injury. The candidate cellular sources of recovery, replacement: adjacent, less damaged tubular cells, resident adult kidney stem/progenitor cells and circulating mesenchymal cells from the bone marrow. Amongst others the following cell surface markers were used for isolating/enriching stem cell/multipotent renal progenitor populations: CD133, stem cell antigen-1 (Sca-1), CD24, CD90, Pax-2, Oct-4, Rex-1 (see table).

One such population was isolated from the cortical interstitium making up 0.8% of all cortical cells and were capable to differentiate into epithelial and endothelial like cells in vitro forming tubular structures in SCID mice [Bussolati et al, 2005]. In the lack of definitive markers of kidney stem cells not much certain could be said on the kidney stem cell niche.

Literature: Gupta S, Rosenberg ME. (200 Do Stem Cells Exist in the Adult Kidney? Am J Nephrol. 19;28(4):607-613

Percy CJ, Power D, Gobe GC. Renal ageing: changes in the cellular mechanism of energy metabolism and oxidant handling. Nephrology (Carlton). 2008 Apr;13(2):147-52.

Bussolati B, Bruno S, Grange C, Buttiglieri S, Deregibus MC, Cantino D, Camussi G. (2005) Isolation of renal progenitor cells from adult human kidney. Am J Pathol. 2005 Feb;166(2):545-55.