bioengineering

Synthetic morphology: applying synthetic biology to anatomy?

Attila Csordas — Mon, 02 Jun 2008 19:45:11 -0700

Description

As far as I understand synthetic morphology = develompental biology +synthetic biology + tissue engineering + anatomy to create new cellular patterns.

Jamie A. Davies: Synthetic morphology: prospects for engineered, self-constructing anatomies

“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.”

Maybe more light could be shed on the topic and approach by comparison to regenerative medicine:

"It should be noted that this approach is quite distinct from the ‘reprogramming’ of stem cells, for example for the purposes of regenerative medicine. The guiding principle of stem cell manipulation is that the genome of these cells already contains the complete ‘genetic programme’ for making all of the cell types in an embryonic and adult body. The (rather poorly chosen) word ‘reprogramming’ is used in this context to mean setting the state of the stem cells to some desired state of their existing developmental–genetic programme (e.g. the state of gene expression that corresponds to being a neural progenitor cell). The principle of the work described in this paper, by contrast, is to create entirely novel genetic programmes that do not already exist in any cell. To be clear, these novel programmes may use basic existing cell biological components common to all cells (e.g. guided self-assembly of actin filaments), but not ‘developmental’ modules that are present in only some times and places in embryos. If a normal mammalian tissue is desired, it is sensible to use stem cell approaches: synthetic morphology is intended to create structures that do not exist in any normal developmental programme. It should also be noted that there is no reason why the development of morphologies in designed systems should be based closely on how similar structures develop in evolved systems when another way would be more efficient. Part of the point of synthetic morphology is that it provides a means of escaping evolved life’s historically fixed constraints."

Biomedical Sciences and Biotechnology

Source

Jamie A. Davies: Synthetic morphology: prospects for engineered, self-constructing anatomies
Journal of Anatomy 212 (6) , 707–719 doi:10.1111/j.1469-7580.2008.00896.x
http://www.blackwell-synergy.com/doi/full/10.1111/j.1469-7580.2008.00896.x?cookieSet=1#

UC San Diego researchers target tumors with tiny 'nanoworms'

Adam Nucci — Tue, 27 May 2008 11:48:28 -0700

NOTE: This content was aggregated from RSS feed. Original source is http://feeds.feedburner.com/~r/NanotechnologyToday/~3/299274078/uc-san-diego-researchers-target-tumors.html

Segmented “nanoworms” composed of magnetic iron oxide and coated with a polymer are able to find and attach to tumors. Credit: Ji-Ho Park, UCSD.
Scientists at UC San Diego, UC Santa Barbara and MIT have developed nanometer-sized “nanoworms” that can cruise through the bloodstream without significant interference from the body’s immune defense system and—like tiny anti-cancer missiles—home in on tumors.

Their discovery, detailed in this week’s issue of the journal Advanced Materials, is reminiscent of the 1966 science fiction movie, the Fantastic Voyage, in which a submarine is shrunken to microscopic dimensions, then injected into the bloodstream to remove a blood clot from a diplomat’s brain.

Using nanoworms, doctors should eventually be able to target and reveal the location of developing tumors that are too small to detect by conventional methods. Carrying payloads targeted to specific features on tumors, these microscopic vehicles could also one day provide the means to more effectively deliver toxic anti-cancer drugs to these tumors in high concentrations without negatively impacting other parts of the body.

“Most nanoparticles are recognized by the body's protective mechanisms, which capture and remove them from the bloodstream within a few minutes,” said Michael Sailor, a professor of chemistry and biochemistry at UC San Diego who headed the research team. “The reason these worms work so well is due to a combination of their shape and to a polymer coating on their surfaces that allows the nanoworms to evade these natural elimination processes. As a result, our nanoworms can circulate in the body of a mouse for many hours.”

“When attached to drugs, these nanoworms could offer physicians the ability to increase the efficacy of drugs by allowing them to deliver them directly to the tumors,” said Sangeeta Bhatia, a physician, bioengineer and a professor of Health Sciences and Technology at MIT who was part of the team. “They could decrease the side effects of toxic anti-cancer drugs by limiting their exposure of normal tissues and provide a better diagnosis of tumors and abnormal lymph nodes.”

The scientists constructed their nanoworms from spherical iron oxide nanoparticles that join together, like segments of an earthworm, to produce tiny gummy worm-like structures about 30 nanometers long—or about 3 million times smaller than an earthworm. Their iron-oxide composition allows the nanoworms to show up brightly in diagnostic devices, specifically the MRI, or magnetic resonance imaging, machines that are used to find tumors.

“The iron oxide used in the nanoworms has a property of superparamagnetism, which makes them show up very brightly in MRI,” said Sailor. “The magnetism of the individual iron oxide segments, typically eight per nanoworm, combine to provide a much larger signal than can be observed if the segments are separated. This translates to a better ability to see smaller tumors, hopefully enabling physicians to make their diagnosis of cancer at earlier stages of development.”

In addition to the polymer coating, which is derived from the biopolymer dextran, the scientists coated their nanoworms with a tumor-specific targeting molecule, a peptide called F3, developed in the laboratory of Erkki Ruoslahti, a cell biologist and professor at the Burnham Institute for Medical Research at UC Santa Barbara. This peptide allows the nanoworms to target and home in on tumors.

“Because of its elongated shape, the nanoworm can carry many F3 molecules that can simultaneously bind to the tumor surface,” said Sailor. “And this cooperative effect significantly improves the ability of the nanoworm to attach to a tumor.”

The scientists were able to verify in their experiments that their nanoworms homed in on tumor sites by injecting them into the bloodstream of mice with tumors and following the aggregation of the nanoworms on the tumors. They found that the nanoworms, unlike the spherical nanoparticles of similar size that were shuttled out of the blood by the immune system, remained in the bloodstream for hours.

“This is an important property because the longer these nanoworms can stay in the bloodstream, the more chances they have to hit their targets, the tumors,” said Ji-Ho Park, a UC San Diego graduate student in materials science and engineering working in Sailor’s laboratory.

Park was the motivating force behind the discovery when he found by accident that the gummy worm aggregates of nanoparticles stayed for hours in the bloodstream despite their relatively large size.

While it’s not clear yet to the researchers why, Park notes that “the nanoworm’s flexibly moving, one dimensional structure may be one the reasons for its long life in the bloodstream.”

The researchers are now working on developing ways to attach drugs to the nanoworms and chemically treating their exteriors with specific chemical “zip codes,” that will allow them to be delivered to specific tumors, organs and other sites in the body.

“We are now using nanoworms to construct the next generation of smart tumor-targeting nanodevices,” said Ruoslahti. We hope that these devices will improve the diagnostic imaging of cancer and allow pinpoint targeting of treatments into cancerous tumors.” ###

Other researchers involved in the development were Michael Schwartz of UC San Diego, Geoffrey von Maltzahn of MIT, and Lianglin Zhang of UC Santa Barbara. The project was funded by grants from the National Cancer Institute of the National Institutes of Health.

Comment: Michael Sailor 858-534-8188 Contact: Kim McDonald kimmcdonald@ucsd.edu 858-534-7572 University of California - San Diego

Future of neuroscience

Novel faultless DNA construction method from imperfect oligonucleotides

Attila Csordas — Wed, 14 May 2008 20:00:52 -0700

Description

A novel recursive DNA construction procedure was reported by scientists from the Weizmann Institute of Science, Rehovot, Israel constructing couple of kilobases long DNA molecules. They are claiming that their method "surpasses existing methods for de novo DNA synthesis in speed, precision, amenability to automation, ease of combining synthetic and natural DNA fragments, and ability to construct designer DNA libraries. It thus provides a novel and robust foundation for the design and construction of synthetic biological molecules and organisms."

From the abstract:

"Making faultless complex objects from potentially faulty building blocks is a fundamental challenge in computer engineering, nanotechnology and synthetic biology. Here, we show for the first time how recursion can be used to address this challenge and demonstrate a recursive procedure that constructs error-free DNA molecules and their libraries from error-prone oligonucleotides. Divide and Conquer (D&C), the quintessential recursive problem-solving technique, is applied in silico to divide the target DNA sequence into overlapping oligonucleotides short enough to be synthesized directly, albeit with errors; error-prone oligonucleotides are recursively combined in vitro, forming error-prone DNA molecules; error-free fragments of these molecules are then identified, extracted and used as new, typically longer and more accurate, inputs to another iteration of the recursive construction procedure; the entire process repeats until an error-free target molecule is formed."

Biomedical Sciences and Biotechnology

Source

Gregory Linshiz, Tuval Ben Yehezkel, Shai Kaplan, Ilan Gronau, Sivan Ravid, Rivka Adar & Ehud Shapiro: Recursive construction of perfect DNA molecules from imperfect oligonucleotides
http://www.nature.com/msb/journal/v4/n1/full/msb200826.html
Molecular Systems Biology 4 Article number: 191 doi:10.1038/msb.2008.26
Published online: 6 May 2008
Citation: Molecular Systems Biology 4:191

Stem Cell Solution? A company claims to have made safer reprogrammed stem cells

Matt Daniels — Mon, 10 Mar 2008 09:31:34 -0700

Description

Stem-Cell Solution?
A company claims to have made safer reprogrammed stem cells
Thursday, February 28, 2008
(Emily Singer, MIT Technology Review)

PrimeGen, a small biotech company based in Irvine, CA, says that it has solved one of the major hurdles in using reprogrammed stem cells for human therapies. Last year, scientists announced that they had successfully created embryonic-like stem cells from adult cells, circumventing the ethical and technical hurdles associated with embryonic stem cells. But the method used viruses to deliver genes, raising concerns over cancer risk.

According to an article in Forbes,

PrimeGen claimed Tuesday it had circumvented this problem. Instead of genes, it uses unspecified carbon-based "delivery particles" to insert four proteins into cells to stimulate the reprogramming process. This caused some of the cells to revert to being much like embryonic stem cells, PrimeGen said. PrimeGen said it has done the experiment with retinal, skin and testicular cells.

"Our goals are ambitious--we believe with this therapy, we can be in clinic in 2010," said PrimeGen president John Sundsmo in an interview. He said he couldn't release details on what the delivery particles are until the company finalizes an agreement with a corporate partner.

However, some scientists are skeptical. Rather than being published in a peer-reviewed scientific journal, the findings were released during a brief presentation at a stem-cell industry conference in New York.

According to Forbes,

Many outside scientists said they weren't familiar with the work and weren't quite sure what to think. "Until the work goes through [peer-review], it would be difficult to evaluate," says James Thomson, the researcher at University of Wisconsin, Madison, who created the first embryonic stem cells in 1998. George Daley, of Harvard University, said he was "pretty suspicious of publication by press release."

Nonetheless, "if this is real it really is a significant step," says Arnold Kriegstein, director of the Institute for Regenerative Medicine at U.C.-San Francisco. "They could be on to something."

Source

Active Biomaterials for Regenerative Medicine

Alex Soojung-Kim Pang — Tue, 23 Oct 2007 11:10:30 -0700

Description

Research on active biomaterials for implantation in the human body could lead to in-situ repair and regeneration of damaged tissue as an alternative to surgery and a cure for some diseases.

The first generation of manufactured biomaterials emerged in the 1960s; they were prosthetic parts made of inert substances that were intended to be placed inside the body with minimal likelihood of immune system rejection. A second generation employed bioactive materials that could elicit a desired action and reaction from the body. Employing research at the molecular level, a new generation of biomaterials is in development; these novel materials are being designed to stimulate specific cellular responses, thereby activating genes to stimulate the regeneration of live tissue. While research on active biomaterials is new, the development of biomaterials has been under way for 40+ years.

If regenerative medicine based on active biomaterials can be developed, it is conceivable that the body will be able to heal itself internally, as it does with a cut or scrape today. Tissue regeneration shows the greatest promise with the use of stem cells, so new developments in stem cell research are an important part of the effort. Nanomaterials may provide solutions to the significant challenge of developing mechanisms that will support blood flow in engineered materials.

Implications:
* Vast enhancement of the human body's ability to repair itself
* Potential for reversal of organ damage resulting from disease
* Decreased use of surgery

Early Indicators:
* Employment of biomaterials for skin regeneration in acute wounds such as burns and as scaffolds for guided nerve regeneration at the Institute for Regenerative Medicine at Wake Forest University
* Successful application of research by Stephan Heller (Harvard/Stanford) on using adult and embryonic stem cells to regenerate hearing tissues, leading to improvement of hearing loss due to aging

What to Watch:
* Breakthroughs in stem cell research, nanomaterials and microtextiles lead to procedures that can be tested in clinical trials.

Parallels/Precedents:
* Development of the first and second generations of manufactured biomaterials

Enablers/drivers:
* Better understanding of the basic mechanisms involved in cell growth and differentiation into different types of tissue
* Resolution of the ethical dilemma associated with the use of embryonic stem cells
* Rapid aging of the population in Western societies, outpacing medicine's ability to perform invasive surgeries and the human and financial resources to do so
* Ongoing nanomaterial research

Signals

Promising Applications of Synthetic Biology

Alex Soojung-Kim Pang — Tue, 23 Oct 2007 11:10:30 -0700

Description

Stretching the realm of possibilities, biological physicists and engineers are treating cells as tools that can be mechanically reworked for environmental and biomedical purposes. Expect new applications in the next 10 to 20 years but also intense debate about unintended consequences.

In the 1970s, with knowledge of genetics growing rapidly, the ability to engineer life was conceived. Three decades later the possibilities for coaxing and crafting microbes to work for us have only expanded, and scientists are making practical headway in the emerging multidisciplinary field of synthetic biology, developing novel biological functions and systems. In this world, biology is a technology, a part, a tool, a machine, a factory, and research topics include genetic network design, biomimetics, energy sources, microfluidics, molecular machines, and biomaterials. In turn, this research has the potential to become the basis for an improved understanding of biology, as it involves creating controlled systems in which biological principles can be tested. Scientists have suggested that the field holds great potential for addressing problems in biomedicine, environmental remediation, and energy supply.

The concept that has shown the greatest early promise is fashioning bacteria into 'biofactories' to produce specific chemicals or biological compounds. Of great significance to global public health, Jay Keasling of the Lawrence Berkeley National Laboratory has engineered a bacteria to produce artemisinin, a compound used to treat malaria. Artemisinin is found naturally in the wormwood plant but is costly to chemically synthesise or harvest. The same methods could theoretically be used to produce cancer drugs, such as Taxol, that are currently expensive.

Others are working on the construction of standardized sequences of DNA, 'biobricks' that could be inserted to produce predictable effects, or a cell that signals how many times it has divided. These projects will help the field develop new tools and methods in the next 3 to 10 years and will set the stage for future applications. New technologies can be expected in the next 10 to 20 years.

Given the debate in the UK regarding genetically modified organisms, this research, that appears to take GM to the next level, has the potential to reignite similar debates and concerns."

This will be enabled by:

"Decreasing cost of DNA sequencing and synthesis
New funding from private foundations, state and federal governments, and private industry
New voluntary safeguards and government regulations addressing public concerns about the new and uncertain research and applications"

Early indicators include:

"Creation in 2000 by Michael Elowitz and Stanislas Leibler, biological physicists, of a genetic circuit that produced a fluorescent protein
Successful completion in 2002 by Eckard Wimmer of a 3-year effort to create a polio virus from scratch
Production in 2004 by Jay Keasling at the Lawrence Berkeley National Laboratory of an antimalaria drug using engineered bacteria
Hosting by MIT in June 2004 of the first conference on synthetic biology
Announcement in December 2004 by the Bill and Melinda Gates Foundation of a $42.5 million grant for research and development in synthetic biology
Opening in 2005 of the Berkeley Center for Synthetic Biology by the California Institute for Quantitative Biomedical Research
Listing in MIT's Technology Review in 2005 of 'bacterial factories' as one of the top 10 emerging technologies"

What to watch:

"Pharmaceutical industry leaders buy up small synthetic biology companies.
Global epidemics such as malaria are eradicated using biologics produced from bacteria.
Public debate grows about the uncertainties and unintended consequences of engineered organisms as new technologies are developed and introduced, and public concern flares up after the first 'biohacker' strike.

Signals

Longest Piece of Synthetic DNA Yet: Scientific American