Introducing Biological Internet-Bi Fi


Bioengineers at Stanford give M13 a makeover

Bioengineering is a really interesting field, specially if we consider the development we come to achieve. The following news comes from Standford university. The researchers have established a proverbial “biological internet” through M13 virus. They are able to send genetic messages using it. The detail can be read below:

If you were a bacterium, the virus M13 might seem innocuous enough. It insinuates more than it invades, setting up shop like a freeloading houseguest, not a killer. Once inside it makes itself at home, eating your food, texting indiscriminately. Recently, however, bioengineers at Stanford University have given M13 a bit of a makeover.

The researchers, Monica Ortiz, a doctoral candidate in bioengineering, and Drew Endy, PhD, an assistant professor of bioengineering, have parasitized the parasite and harnessed M13’s key attributes — its non-lethality and its ability to package and broadcast arbitrary DNA strands — to create what might be termed the biological Internet, or “Bi-Fi.” Their findings were published online Sept. 7 in the Journal of Biological Engineering.

Using the virus, Ortiz and Endy have created a biological mechanism to send genetic messages from cell to cell. The system greatly increases the complexity and amount of data that can be communicated between cells and could lead to greater control of biological functions within cell communities. The advance could prove a boon to bioengineers looking to create complex, multicellular communities that work in concert to accomplish important biological functions.

The Mechanism

M13 is a packager of genetic messages. It reproduces within its host, taking strands of DNA — strands that engineers can control — wrapping them up one by one and sending them out encapsulated within proteins produced by M13 that can infect other cells. Once inside the new hosts, they release the packaged DNA message.

The M13-based system is essentially a communication channel. It acts like a wireless Internet connection that enables cells to send or receive messages, but it does not care what secrets the transmitted messages contain.

“Effectively, we’ve separated the message from the channel. We can now send any DNA message we want to specific cells within a complex microbial community,” said Ortiz, the first author of the study.

It is well-known that cells naturally use various mechanisms, including chemicals, to communicate, but such messaging can be extremely limited in both complexity and bandwidth. Simple chemical signals are typically both message and messenger — two functions that cannot be separated.

“If your network connection is based on sugar then your messages are limited to ‘more sugar,’ ‘less sugar,’ or ‘no sugar’” explained Endy.

Cells engineered with M13 can be programmed to communicate in much more complex, powerful ways than ever before. The possible messages are limited only by what can be encoded in DNA and thus can include any sort of genetic instruction: start growing, stop growing, come closer, swim away, produce insulin and so forth.

The Bandwidth

In harnessing DNA for cell-cell messaging the researchers have also greatly increased the amount of data they can transmit at any one time. In digital terms, they have increased the bit rate of their system. The largest DNA strand M13 is known to have packaged includes more than 40,000 base pairs. Base pairs, like 1s and 0s in digital encoding, are the basic building blocks of genetic data. Most genetic messages of interest in bioengineering range from several hundred to many thousand base pairs.

Ortiz was even able to broadcast her genetic messages between cells separated by a gelatinous medium at a distance of greater than 7 centimeters.

“That’s very long-range communication, cellularly speaking,” she said.

Down the road, the biological Internet could lead to biosynthetic factories in which huge masses of microbes collaborate to make more complicated fuels, pharmaceuticals and other useful chemicals. With improvements, the engineers say, their cell-cell communication platform might someday allow more complex three-dimensional programming of cellular systems, including the regeneration of tissue or organs.

“The ability to communicate ‘arbitrary’ messages is a fundamental leap — from just a signal-and-response relationship to a true language of interaction,” said Radhika Nagpal, professor of computer science at the Wyss Institute for Biologically Inspired Engineering at Harvard University, who was not involved in the research. “Orchestrating the cooperation of cells to form artificial tissues, or even artificial organisms is just one possibility. This opens a door to new biological systems and solving problems that have no direct analog in nature.”

Ortiz added: “The biological Internet is in its very earliest stages. When the information Internet was first introduced in the 1970s, it would have been hard to imagine the myriad uses it sees today, so there’s no telling all the places this new work might lead.”

-Adeel

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Why people crave chocolates


Brain chemicals causing craving for chocolates by Maria Atia

 On 20th September, 2012 a research report was published in a Cell Press publication, Current Biology, in which factors involved in the passion for eating chocolate has been explained. Like drugs and some medicines, chocolates have also been known to be an addiction for people. Once you get in the habit of eating chocolates it becomes difficult to resist them. But have you ever thought why it happens so that you crave for chocolate so often? Alexandra DiFeliceantonio of the University of Michigan, Ann Arbor thought about this.

DiFeliceantonio and her team used rats for her study on chocolate cravings. What she did was that she artificially introduced a chemical or drug into the body of rats which straight away entered the brain. The drug was targeted for a special brain portion called neostriatum. This brain part was previously thought to be important for movement but this study has changed things. When DiFeliceantonio introduced this drug in rats their consumption of M&M’s increased two fold than normal.

According to DiFeliceantonio, the older explanations for these cravings are no longer viable and the brain system gets more complicated on this note. She also said that it may because of the production of this drug that people consume more chocolate then required. A substitute for the drug being produced in brain has been found to be in a chemical called enkephalin. It was because of the over production of this chemical in the neostriatum that rats ate more chocolate.

The drug produced in neostriatum acts in a way to increase the desire and crave of rats for chocolate instead of producing likeness of chocolate in rats. Following similar lines of this drug the eating habits of humans will now become easy to be explained. In her report she has also mentioned that the same drug has been detected in that part of the brain in people with drug addiction and in obese people wanting food and sweets.

The next research in line is to find ways to stop this want for chocolate and sweets. This will help you to pass by your favorite food item even if you see it.

-Maria

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Google to invest more in biotech


Google VC to invest in Biotech by Muhammad Adeel

Google has a habit of doing big things and now Google Ventures is aiming to invest in biotech entrepreneurs as well. The venture capital front of the search engine giant is aiming to make life sciences a main area of investment in the coming 5 years. The amount that has been allocated for this venture is in reported to be $1 Billion!

This approach of Google Ventures was announced by the Managing Partner, William Maris during his appearance at CNBC. He cited that the venture front is willing to take on risky fronts like cryogenics and nanotechnology as well. Furthermore, they intend to fund pharmaceutical companies that are developing cancer drugs as well. This is being said, this is not for the first time that Google has invested in biotech. They have invested in more than 100 companies. The group has backed the antibody-discovery outfit Adimab (a 2010 Fierce 15 company), Foundation Medicine, a personalized cancer diagnostics group, and the life sciences software firm DNAnexus, to name a few.

It’s been a positive development in biotech because a number of other VC groups have reduced their bets in the sector or pulled out altogether. Backing a biotech often requires long commitments from VC groups and plenty of capital–both of which Google Ventures can deliver. “There’s a whole world of innovation out there outside of social media. It’s a huge growth area, but we’re investing a lot of money in life sciences,” Maris said, as quoted by CNBC.com. He also noted that his group seeks to fund entrepreneurs with “a healthy disregard for the impossible.

-Adeel

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Breathing Nanotubes


NanoTubes: The next step in drug delivery by Muhammad Adeel

While nanotechnology has offered a lot to us in the domain of medical technology, its main potential is still to be recognized. A recent development tells us that flexible self-assembled nanotubes have been made. This remarkable feat has been accomplished by researchers at Seoul National University. They have done this task with the help of macromolecules that on one end are hydrophobic, while the other end is hydrophilic. This arrangement would help make a self-assembly when placed in an aqueous solution. Furthermore, these nanotubes would contract and expand as per the change in temperature, hence you have breathing nanotubes!

Chemistry of the nanotubes

An interesting element is that no covalent bonds are holding these nanotubes together. Not being held together by the covalent bonds allows these nanotubes to attain the flexibility that is required to function appropriately. A change in temperature would change the size of the nanotubes by a size of 3 to 4 nanometers. With lowering temperature, the nanotubes increased their size and increasing the temperature had a reverse effect. This response is similar to those of blood vessel, as explained by Dr. Myongoo Lee-the lead author.

This is better explained by the image below:

Images showing the expanded (P twist) and contracted (M twist) forms of the nanotubules. (Courtesy: Science)

Potential Benefits

One of the main benefits of these nanotubes is that they could be used to “pack” drugs and used as effective drug delivery methods. They would only be delivered in the designated area and pose no side effects in the proximity.

To test these tubes, light sensitive fullerene particles were used. They have been used in cancer therapy and also in solar panels as well. The uptake was aided by the fact that these fullerene particles are hydrophobic in nature. The researchers were able to demonstrate that more packing was observed when the tubes were contracted. More contraction resulted in expulsion of some fullerenes.

Another benefit of these nanotubes is that they can be used as templates for various nanostructures. Their usage as templates could allow better usage of nanotubes at large.

The mechanism

The tubes are different from previous ones on the account that they are not assembled through covalent bonding or via hydrogen bonds. One of the problems with such a structure was that no flexibility could be attained. Dr. Lee and his team were able to circumvent this with the help of a 6 bent shaped molecule, which could serve as their building block. Hexameric rings are formed which allow the sliding mobility.

As stressed earlier, a major benefit of these nanotubes is that they have flexibility and can also serve as templates. Via this usage, it is possible to transform the nanostructure properties as well. The properties like conductivity and magnetism can be controlled at our discretion.

The Challenge

While this is a great development in the domain of nanotech and drug delivery, it is yet to be seen whether this structure is effective at large or not. So far, the researchers tested it with fullerene only. Other materials and molecules also need to be tested.

Reference of article: Z. Huang et al., “Pulsating tubules form noncovalent macrocycles,” Science, 337:1521-1526, 2012.

-Adeel

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Ultrasound: A drug delivery system


Ultrasound waves as a transdermal drug delivery system by Amina Shakrullah

In another remarkable achievement of MIT engineers, the researchers have boosted the permeability of skin for drugs by using ultrasound waves. By this success the transdermal drug delivery system will become more efficacious. The MIT researchers are sanguineous that the extraordinary achievement can pave the way for needle free vaccinations and noninvasive drug delivery. An MIT graduate in chemical engineering and also among the leading authors of the paper, Carl Schoellhammer said this technology will be helpful for topical drugs as steroids and cortisol. At the same time equally efficient for systemic drugs and proteins such as insulin and antigens for vaccination.

In a transient and pain free affect the ultrasound waves, sound waves having frequencies greater than the upper limit of human hearing; lightly wear away upper skin layer, which in turn will increase the skin permeability. The researchers found if two separate ultrasound beams, one with low frequency and other with high frequency are applied to skin, uniformly boost skin permeability across a skin region. The two beams enhance skin permeability more rapidly as compared to a single ultrasound beam.

Basic principle:

Ultrasound waves generate chaotically moving tiny bubbles while traveling through a fluid. When bubbles reach up to a certain point they become unstable and implode. As a result surrounding fluid will suddenly move towards the empty space. As a result creates high speed “microjets” of fluid that will lead to microscopic abrasions on the skin. So, in the given scenario researchers use fluid to deliver drugs. In recent years the researchers have focused on low frequency ultrasound waves for enhancing transdermal drug delivery system. The reason of using low frequency sound waves is that high frequency waves do not have enough energy to implode the bubble and produce scattered abrasions and random spots in the treated area.

But the MIT engineers found that the combination of high and low energy ultrasound waves give better results. The bubbles generated by high frequency waves are popped up by low frequency waves. According to Samir Mitragorti a chemical engineering professor at the University of California Santa Barbara, to improve the technology it is a very innovative way. It will help to increase the amount of drug delivered through the skin and at the same time will expand the types of drugs that can be delivered through the skin. To evaluate and compare the efficiency of the technology with the previous one’s the researchers use pig skin. The results showed that the permeability was boosted and was much more than the single frequency system.

Noninvasive drug delivery system:

This type of unique drug delivery system can be used to deliver any kind of drug, which is currently administered as capsules. This drug delivery system can be used to treat skin conditions such as acne and psoriasis. It is also helpful to enhance transdermal patches which are already in use such as nicotine patches. The researchers are of the opinion that this system promises a noninvasive for diabetics to control the blood sugar levels by short and long term delivery of insulin. The method can also be used as needle free and pain free vaccination administering system. The developers of the technology are hopeful that the system will pass the safety tests as FDA has already approved single frequency ultrasound transdermal system.

-Amina

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Nano Electrodes put to use


Nano-electrodes used to study the presence of ROS/RNS by Maria Atia

Whenever a foreign particle enters a macrophage or B-cell it is trapped by the cell inside a vesicle. Both these cells are phagocytes involved in degrading unwanted material present in the cell. The vesicle then merges with a lysosome, another kind of vesicle present inside the cell and which has the capability to degrade the foreign particle. The lysosome contains reactive oxygen and nitrogen species (ROS/RNS) which destroy and degrade the foreign particle. This whole process intrigued the scientists to think whether any reactive oxygen or nitrogen molecule got released into the cytoplasm during the whole process.

Michael Mirkin from the City University of New York, Queens College and his colleagues from Université Pierre at Marie Curie initiated to study this process. So far microelectrodes have been used to study the actual processes of inter-cell signaling, factor secretion and other similar extracellular events, also known as real-time biochemistry. But the disadvantage of microelectrodes is that they cannot be used to study intracellular process.

Adapting the concept of microelectrodes, Mirkin and his colleagues designed Nano-electrodes to study the intra-cellular process. Platinum was used on bigger electrodes to detect the presence of reactive oxygen and nitrogen species. Likewise platinum black was used on the Nano- electrodes. Platinum black is similar to the normal platinum but is the high-surface area version of the normal platinum.

Adrian Michael, University of Pittsburgh, though not a part of this research, shared his views on this research. He said that it may sound very easy to make a smaller version of the electrodes but is rather quite difficult to do so. He also said that the making of these Nano- electrodes requires high precision and accuracy along with the use of atomic force microscope so that the whole manufacturing of electrodes process could be monitored closely, as mentioned in the published paper.

What Mirkin and his colleagues did in their research was that they inserted the Nano-size electrode into the cell without damaging the cell wall. Then they induced vesicle formation in the cell by pinching it a little. As soon as the vesicle united with the lysosome, the release of reactive oxygen and nitrogen molecules was detected in the cytoplasm by the electrodes, although it happened for a very minute second. The materials of the vesicle excreted out of the cell were detected a few seconds later by the microelectrode present in the vicinity of the phagocytic cell.

Thus Mirkin said that it is important to make sure that the geometry or shape of the electrode is absolute proper so that the cell does not get damaged. He used the atomic force microscope to monitor the platinum coating process of the electrode. Only the electrodes which received clearance were further employed in detecting the presence of ROS/RNS in the macrophages and B-cells. The only problem to be dealt with in this whole procedure is the dimensions and performance of the tip as both may get changed with time.

From the experiments it was thus found that the leak of ROS/RNS from the lysosome is cleared in less than a second’s time so that the cell toxicity level does not rises too high. This helps the cell in surviving the leak. Mirkin also said while sharing his views that the same concept of Nano-electrodes could be employed to study other cells experiencing oxidative stress. He said that it will help us to understand certain “disease states” caused due to the oxidative stress.

-Maria

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DNA twists and Gene Regulation


Coiling gets more complicated in the DNA by Maria Atia

60 years have passed since the double helix was discovered first and still new advancements are being made on the basic features and properties of DNA, said Cees Dekker of Delft University of Technology. Dekker and his colleagues published their research in Science recently in which they have pointed out that the supercoils present in the DNA double helix jump along the DNA. This research will help the scientists to understand more about the DNA organization and the gene regulation processes undergoing in the cell.

Ralf Seidel of University of Technology Dresden sharing his opinion on this research although not involved in the project said that this research is the first of its kind which deals with the changing aspects of DNA supercoils. He also said that the hopping motion of the DNA supercoils helps in bringing DNA sites closer to one another. Seidel’s area of study are the molecular motor proteins which along the DNA.

There are two types of coiling present in the DNA. One in which the strand coils around itself and the second in which the DNA double helix coils as a whole. The extra-twisted coils are known as plectonemes. The histone proteins, packed along with the DNA, play a very important role in the packing of a long DNA strand into the tiny space in the nucleus of the cell. The coiling is disturbed when certain proteins like transcription factors are in working position because they can’t work if the DNA is coiled and uncoil the DNA for their working. Because of supercoiling of the DNA many parts of the DNA which are present at a distance in a straight DNA come closer in the twisted DNA and it is thought to affect the expression of genes.

In their research Dekker and his colleagues instead of working on both the DNA strands at the same time took a single DNA strand and twisted it artificially by attaching one end of the DNA to a glass capillary tube and the other to a magnetic bead. Then they microscopic magnets to introduce coils in the DNA strand. The DNA was fluorescently labeled and this fluorescence helped the scientists to study the movement of supercoils using fluorescence microscopy. Through this method it was revealed on them that the supercoils use two ways for moving. They either gradually move along the DNA strand or vanish from one location and appear at another location. No reason for this hopping pattern of the supercoils has been found so far.

Prashant Purohit studying DNA behavior in University of Pennsylvania said that the hopping nature of the supercoils is even more complicated and confusing than the diffusing method that the supercoils use. He also said that this behavior of the supercoils is not confined to any one location on the DNA but has equal effect on the whole DNA.

Dekker’s study which was done in a singly-valent ion environment showed that the supercoil formation occurred at very low concentration of such ions. But it is expected that the DNA supercoils will form differently in a different ionic environment. For example the coiling and condensation of the DNA may be more when the ions in the surrounding environment having 3 or more positive charges.

As the study has been on only one DNA strand thus it is impossible to say that how the supercoils move about when in the double helix form packed with proteins inside the cell.  Bryan Daniels said that it may be so that this behavior of supercoils has more importance in the DNA of prokaryotic cells because it is less condensed as compared to the eukaryotic DNA which is highly condensed and packed. Daniels is involved in the modeling of biological systems at the Wisconsin Institute for Discovery at the University of Wisconsin-Madison.

To study the supercoiling motion in vivo in eukaryotic cells Dekker and his colleagues are trying to study the effects on supercoiling of the different DNA sequences and the presence of DNA binding proteins, both their sequences and their position.

-Maria

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