Artificial jellyfish built from rat cells.

I came across this article while looking for a published paper. This unusual concept caught my attention, so I thought I would share it with everyone :).

Bioengineers have made an artificial jellyfish using silicone and muscle cells from a rat’s heart. The synthetic creature, dubbed a medusoid, looks like a flower with eight petals. When placed in an electric field, it pulses and swims exactly like its living counterpart.

“Morphologically, we’ve built a jellyfish. Functionally, we’ve built a jellyfish. Genetically, this thing is a rat,” says Kit Parker, a biophysicist at Harvard University in Cambridge, Massachusetts, who led the work. The project is described today in Nature Biotechnology1.

Parker’s lab works on creating artificial models of human heart tissues for regenerating organs and testing drugs, and the team built the medusoid as a way of understanding the “fundamental laws of muscular pumps”. It is an engineer’s approach to basic science: prove that you have identified the right principles by building something with them.

 

A jellyfish made of silicone and rat heart cells ‘swims’ in water when subjected to an electric field. In 2007, Parker was searching for new ways of studying muscular pumps when he visited the New England Aquarium in Boston, Massachusetts. “I saw the jellyfish display and it hit me like a thunderbolt,” he says. “I thought: I know I can build that.” To do so, he recruited John Dabiri, a bioengineer who studies biological propulsion at the California Institute of Technology (Caltech) in Pasadena. “I grabbed him and said, ‘John, I think I can build a jellyfish.’ He didn’t know who I was, but I was pretty excited and waving my arms, and I think he was afraid to say no.”

Janna Nawroth, a graduate student at Caltech who performed most of the experiments, began by mapping every cell in the bodies of juvenile moon jellies (Aurelia aurita) to understand how they swim. A moon jelly’s bell consists of a single layer of muscle, with fibres that are tightly aligned around a central ring and along eight spokes.

To make the bell beat downwards, electrical signals spread through the muscle in a smooth wave, “like when you drop a pebble in water”, says Parker. “It’s exactly like what you see in the heart. My bet is that to get a muscular pump, the electrical activity has got to spread as a wavefront.”

Form and function.

Nawroth created a structure with the same properties by growing a single layer of rat heart muscle on a patterned sheet of polydimethylsiloxane. When an electric field is applied across the structure, the muscle contracts rapidly, compressing the medusoid and mimicking a jellyfish’s power stroke. The elastic silicone then pulls the medusoid back to its original flat shape, ready for the next stroke.

When placed between two electrodes in water, the medusoid swam like the real thing. It even produced water currents similar to those that wash food particles into jellyfish’s mouths. “We thought if we’re really good at this, we’re going to recreate that vortex, and we did,” says Parker. “We took a rat apart and rebuilt it as a jellyfish.”

“I think that this is terrific,” says Joseph Vacanti, a tissue engineer at Massachusetts General Hospital in Boston. “It is a powerful demonstration of engineering chimaeric systems of living and non-living components.”

Parker says his team is taking synthetic biology to a new level. “Usually when we talk about synthetic life forms, somebody will take a living cell and put new genes in. We built an animal. It’s not just about genes, but about morphology and function.”

The team now plans to build a medusoid using human heart cells. The researchers have filed a patent to use their design, or something similar, as a platform for testing drugs. “You’ve got a heart drug?” says Parker. “You let me put it on my jellyfish, and I’ll tell you if it can improve the pumping.”

They also hope to reverse-engineer other marine life forms, says Parker. “We’ve got a whole tank of stuff in there, and an octopus on order.”

Published Paper #2

Article reference: Shen, Helen. 2012. “Enzymes grow artificial DNA” Accessed March 31, 2013. http://www.nature.com/news/enzymes-grow-artificial-dna-1.10487#/b1

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DNA, commonly known as the blueprint of life, is the naturally occurring hereditary material in humans and almost all organisms; or so we thought. Scientists have developed lab made alternatives of DNA. These variants act much like DNA in which these mechanisms allow it to store and transfer hereditary information. Then again why should these synthetic strands be crafted? According to Philipp Holliger, a synthetic biologist at the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK, he states that these lab assembled DNA backbones can aid in the development of new drugs and nanotechnologies.

The proposition.

The construction of DNA composes of nucleic acid bases- A, C, G and T assembled on a phosphate and sugar deoxyribose backbone. These replicated polymers known as XNA’s carry the same lettered sequencing except for its backbone which is made of different sugars from the novel DNA molecules. Another biochemist, Gerald Joyce explained that while this task has been attempted before, they were unable to make additional copies these already generated XNA strands. However, recent developments have supplied a way, and a considerable one at that, says Eric Kool, a chemist at Stanford University in California. As a result, the successive DNA to XNA transmission have permitted researches to select the XNA’s that are attached to choice target proteins from a vast number of samples.

Innovation.

With the progression of such research, similar undertakings were undergone. Steven Banner, a biochemist at the Foundation for Applied Molecular Evolution in Florida, together with his associates have simulated polymers with additional artificial genetic lettering on an original DNA backbone. This synthetic sequencing can merge with the modified XNA backbone creating a structure resistant to chemical degradation.

The next step.

Upon further exploration, Biotechnologists may have discovered tools such as polymers that can bind and inhibit proteins, in these evolvable XNA’s. One such example includes strains involved in macular degeneration, a disease which affects older adults resulting in loss of vision in the center of the macula due to retinal damage.

Historical ingenuity put to use.

DNA and RNA, as simple as they may seem to be comprised of, are difficult to produce. Many researchers believe that another simpler molecule was derived first. The TNA3 molecule was developed by Albert Eschenmoser in the year 2000. This strand was in essence a XNA together with a α-l-threofuranosyl nucleic acid backbone and 1 of the 6 polymers used in the study.  This experiment exhibited that the TNAcould conform to the DNA by twisting into a double-helix spiral. Ramanarayanan Krishnamurthy, a leading synthetic organic chemist, noted that the enzymes produced by Holliger advanced past research “by leaps and bounds”. He stated that these developed enzymes confirm that DNA can indeed trade information efficiently with TNA and additional polymers apart from RNA.

Although the XNA’s are dependent on DNA derived enzymes to replicate, researchers can presently duplicate artificial genes resistant to biodegradation.

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Published paper #1

Article:  Dolgin, Elie. 2013. “Antibody drugs set to revive flagging migraine target”. Accessed April 4th, 2013. http://www.nature.com/nrd/journal/v12/n4/full/nrd3991.html

 

I chose this article to analyze as my published paper #1 since this topic is all too familiar to me, as I myself have suffered with headaches and migraines since the age of 14; 7 years to date. I have researched intensely into this topic hoping for a solution to my own migraines.

This article first begins with the story of Emily S. who began experiencing headaches at age 7. Emily is now 31 years old and her headaches have now turned into severe migraines. Over these 24 years, she has tried a variety of prophylactic cures, none of which proved successful in alleviating her migraines. A prophylactic is a medication or a treatment designed and used to prevent a disease from occurring. These treatments used the anticonvulsant drug, Topiramate. However this drug caused short term memory loss and nausea. This combination of a tricyclic antidepressant and a beta blocker has deemed futile to these attacks.

The initial mechanism.

Statistics show that more than 10% of adults in the world experience unbearable migraine headaches. Even though 40% of “migraineurs” are good contenders for therapeutic prophylactic methods, only 1 in 3 of these people receives it. Four monoclonal antibodies (mAbs), currently in Phase I & II, are used to treat these patients, in hope that a problem plagued drug target is what is needed for permanent relief of this problem. These mAbs ultimately hinder the signaling of calcitonin gene-released peptide (CGRP). CGRP is a 37-amino-acid neuropeptide expelled by primary sensory neurons in the trigeminal ganglion during migraine episodes.

Developments.

Small molecule CGRP receptor antagonists have been in development for over a decade. A telcagepant, formulated by Merck & Co. was an investigational drug for the acute treatment and prevention of migraine. This drug gained recognition when it proved to exhibit results superior to placebo when it was used as an abortive therapy in Phase III trials. A placebo effect occurs when a treatment with no known effectiveness, such as a dummy pill, is given to a patient and the patient nevertheless has subsequent improvement in symptoms.  However, the company terminated the development of the drug due to escalated liver enzyme transaminase levels in patients that used the drug over an extended period. Nevertheless the trend of using injectable, prophylactic mAbs directed at CGRP or the CGRP receptor is flourishing.

Advancements.

By 2011, companies such as Amgen and Arteaus Therapeudics began testing new routes for the drug to target; the mAb directed at the CGRP peptide itself. Most recently, in January of 2013, Labrys licensed their drug to the renowned Pfizer Company. They postulated the dosage of once a month. “An antibody with a long half-life” said Alder’s pharmacists, a competing firm. Since the antibodies were not chemically similar to CGRP but instead blocked it, there would be no trace of liver problems.

Concerns.

Fears stemmed from the concern that the CGRP-directed mAbs would not cross the blood-brain barrier (BBB). This simply meant that the drug might not have a significant effect on the neurons in the brain. This apprehension was quickly dismissed on the view that both the peripheral and central systems could be stimulated instead of either or. Another issue was the presence of side effects. Due to CGRP’s ability to heal wounds easily, neuroscientists pondered upon the consequences of depleting the peptide and its long term effects. In the end it was decided that the drug would only prosper after the clinical benefits and injuries were evaluated, with the advantages outweighing the disadvantages. Despite the drug’s high cost of production, it earned more 10,000 times more than its initial cost in profits. In conclusion, the drug proved worthwhile for companies such as Artaeus amidst of generic market of mAbs.

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