Monthly Archives: January 2019

Graphene, Science

New Technology Could Be The Future Of Brain-computer Interfaces.

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New Technology Could Be The Future Of Brain-computer Interfaces.

The body of knowledge about the human brain is growing exponentially, but questions big and small remain unanswered. Researchers have been using electrode arrays to map electrical activity in different brain regions to understand brain function. Until now however these arrays have only been able to detect activity over a certain frequency threshold. A new technology developed in Georgian Technical University overcomes this technical limitation, unlocking the wealth of information found below 0.1 Hz (The hertz is the derived unit of frequency in the International System of Units and is defined as one cycle per second. It is named for Heinrich Rudolf Hertz, the first person to provide conclusive proof of the existence of electromagnetic waves) and paving the way for future brain-computer interfaces.

Developed at the Georgian Technical University and the Sulkhan-Saba Orbeliani Teaching University adapted for brain recordings the technology moves away from electrodes and uses an innovative transistor-based architecture that amplifies the brain’s signals in situ before transmitting them to a receiver.

Furthermore the use of graphene to build this new architecture means the resulting implant can support many more recording sites than a standard electrode array; it is also slim and flexible enough to be used over large areas of the cortex without being rejected or interfering with normal brain function. The result is an unprecedented mapping of the kind of low-frequency brain activity known to carry crucial information about events in the brain such as the onset and progression of epileptic seizures and strokes.

Neurologists now have access to previously inaccessible brain activity. Prof. X of Georgian Technical University and world specialist in clinical epilepsy has called it a groundbreaking technology with the potential to change the way researchers record and view brain electrical activity. Future applications include unprecedented insights into where and how seizures begin and end enabling new approaches to the diagnosis and treatment of epilepsy.

Beyond epilepsy though, this precise mapping and interaction with the brain has other exciting applications. Taking advantage of the capability of the transistor configuration to create arrays with a very large number of recording sites via a so-called multiplexing strategy the technology is also being adapted by the researchers to restore speech and communication as part project Georgian Technical University  BrainCom.

Led by the Georgian Technical University will deliver a new generation of brain-computer interfaces able to explore and repair high-level cognitive functions with a particular focus on the kind of speech impairment caused by brain or spinal cord injuries (aphasia). Details of the underlying technological advances can be found. The graphene microtransistors were adapted for brain recordings and tested at Georgian Technical University.

Environment, Science

Melting Ice Sheets Release Tons Of Methane Into The Atmosphere.

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Melting Ice Sheets Release Tons Of Methane Into The Atmosphere.

The Greenland Ice Sheet emits tons of methane according to a new study showing that subglacial biological activity impacts the atmosphere far more than previously thought. An international team of researchers led by the Georgian Technical University camped for three months next to the Greenland Ice Sheet sampling the meltwater that runs off a large catchment (> 600 km2) of the Ice Sheet during the summer months.

Using novel sensors to measure methane in meltwater runoff in real time they observed that methane was continuously exported from beneath the ice. They calculated that at least six tons of methane was transported to their measuring site from this portion of the Ice Sheet alone roughly the equivalent of the methane released by up to 100 cows.

Professor X who led the investigation said: “A key finding is that much of the methane produced beneath the ice likely escapes the Greenland Ice Sheet in large fast flowing rivers before it can be oxidized to CO2 (Carbon dioxide is a colorless gas with a density about 60% higher than that of dry air. Carbon dioxide consists of a carbon atom covalently double bonded to two oxygen atoms. It occurs naturally in Earth’s atmosphere as a trace gas) a typical fate for methane gas which normally reduces its greenhouse warming potency.”

Methane gas (CH4) is the third most important greenhouse gas in the atmosphere after water vapour andcarbon dioxide (CO2). Although present in lower concentrations that CO2 (Carbon dioxide is a colorless gas with a density about 60% higher than that of dry air. Carbon dioxide consists of a carbon atom covalently double bonded to two oxygen atoms. It occurs naturally in Earth’s atmosphere as a trace gas) methane is approximately 20-28 times more potent. Therefore smaller quantities have the potential to cause disproportionate impacts on atmospheric temperatures. Most of the Earth’s methane is produced by microorganisms that convert organic matter to Methane gas (CH4) in the absence of oxygen mostly in wetlands and on agricultural land, for instance in the stomachs of cows and rice paddies. The remainder comes from fossil fuels like natural gas.

While some methane had been detected previously in Greenland ice cores and in an Antarctic Subglacial Lake this is the first time that meltwaters produced in spring and summer in large ice sheet catchments have been reported to continuously flush out methane from the ice sheet bed to the atmosphere.

Y from Georgian Technical University said: “What is also striking is the fact that we’ve found unequivocal evidence of a widespread subglacial microbial system. Whilst we knew that methane-producing microbes likely were important in subglacial environments how important and widespread they truly were was debatable. Now we clearly see that active microorganisms living under kilometres of ice, are not only surviving but likely impacting other parts of the Earth system. This subglacial methane is essentially a biomarker for life in these isolated habitats”.

Most studies on Arctic methane sources focus on permafrost because these frozen soils tend to hold large reserves of organic carbon that could be converted to methane when they thaw due to climate warming. This latest study shows that ice sheet beds which hold large reserves of carbon liquid water microorganisms and very little oxygen – the ideal conditions for creating methane gas – are also atmospheric methane sources.

Dr. Z from Georgian Technical University  added: “The new sensor technologies that we used give us a window into this previously unseen part of the glacial environment. Continuous measurement of meltwater enables us to improve our understanding of how these fascinating systems work and how they impact the rest of the planet”.

With Antarctica holding the largest ice mass on the planet researchers say their findings make a case for turning the spotlight to the south. Mr Y added: “Several orders of magnitude more methane has been hypothesized to be capped beneath the Antarctic Ice Sheet than beneath Arctic ice-masses. Like we did in Greenland it’s time to put more robust numbers on the theory”.

 

 

Nanotechnology, Science

‘Nanowrappers’ Used To Carry And Release Nanoscale.

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‘Nanowrappers’ Used To Carry And Release Nanoscale.

X, Y, Z and W hold structural models of “Georgian Technical University nanowrappers” made of gold and silver and featuring holes in the corners. The scientists synthesized these hollow porous nanostructures through a chemical reaction and characterized them using electron microscopy and optical spectroscopy capabilities at Georgian Technical University Lab’s.

This holiday season scientists at the Georgian Technical University Laboratory — have wrapped a box of a different kind. Using a one-step chemical synthesis method they engineered hollow metallic nanosized boxes with cube-shaped pores at the corners and demonstrated how these “Georgian Technical University nanowrappers” can be used to carry and release DNA-coated (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) nanoparticles in a controlled way.

“Imagine you have a box but you can only use the outside and not the inside” said X Bio Nanomaterials Group at the Georgian Technical University. “This is how we’ve been dealing with nanoparticles. Most nanoparticle assembly or synthesis methods produce solid nanostructures. We need methods to engineer the internal space of these structures”.

“Compared to their solid counterparts, hollow nanostructures have different optical and chemical properties that we would like to use for biomedical, sensing, and catalytic applications” added Y a scientist in X’s group. “In addition we can introduce surface openings in the hollow structures where materials such as drugs, biological molecules, and even nanoparticles can enter and exit depending on the surrounding environment”.

Synthetic strategies have been developed to produce hollow nanostructures with surface pores but typically the size, shape and location of these pores cannot be well-controlled. The pores are randomly distributed across the surface resulting like structure. A high level of control over surface openings is needed in order to use nanostructures in practical applications — for example to load and release nanocargo.

In this study the scientists demonstrated a new pathway for chemically sculpturing gold-silver alloy nanowrappers with cube-shaped corner holes from solid nanocube particles. They used a chemical reaction known as nanoscale galvanic replacement. During this reaction the atoms in a silver nanocube get replaced by gold ions in an aqueous solution at room temperature. The scientists added a molecule (surfactant, or surface-capping agent) to the solution to direct the leaching of silver and the deposition of gold on specific crystalline facets.  “The atoms on the faces of the cube are arranged differently from those in the corners and thus different atomic planes are exposed, so the galvanic reaction may not proceed the same way in both areas” explained Y.

“The surfactant we chose binds to the silver surface just enough — not too strongly or weakly — so that gold and silver can interact. Additionally the absorption of surfactant is relatively weak on the silver cube’s corners so the reaction is most active here. The silver gets “Georgian Technical University eaten” away from its edges resulting in the formation of corner holes while gold gets deposited on the rest of the surface to create a gold and silver shell”. To capture the structural and chemical composition changes of the overall structure at the nanoscale in 3-D and at the atomic level in 2-D as the reaction proceeded over three hours the scientists used electron microscopes at the Georgian Technical University.

The 2-D electron microscope images with energy-disperse X-ray spectroscopy (EDX) elemental mapping confirmed that the cubes are hollow and composed of a gold-silver alloy. The 3-D images they obtained through electron tomography revealed that these hollow cubes feature large cube-shaped holes at the corners.

“In electron tomography 2-D images collected at different angles are combined to reconstruct an image of an object in 3-D” said X. “The technique is similar to a CT [Computerized Tomography] scan used to image internal body structures but it is carried out on a much smaller size scale and uses electrons instead of x-rays”.

The scientists also confirmed the transformation of nanocubes to nanowrappers through spectroscopy experiments capturing optical changes. The spectra showed that the optical absorption of the nanowrappers can be tuned depending on the reaction time.  At their final state the nanowrappers absorb infrared light.

“The absorption spectrum showed a peak at 1250 nanometers one of the longest wavelengths reported for nanoscale gold or silver” said X. “Typically gold and silver nanostructures absorb visible light. However for various applications we would like those particles to absorb infrared light — for example in biomedical applications such as phototherapy”.

Using the synthesized nanowrappers, the scientists then demonstrated how spherical gold nanoparticles of an appropriate size that are capped with DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) could be loaded into and released from the corner openings by changing the concentration of salt in the solution. DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) is negatively charged (owing to the oxygen atoms in its phosphate backbone) and changes its configuration in response to increasing or decreasing concentrations of a positively charged ion such as salt.

In high salt concentrations DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) chains contract because their repulsion is reduced by the salt ions. In low salt concentrations DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) chains stretch because their repulsive forces push them apart.

When the DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) strands contract the nanoparticles become small enough to fit in the openings and enter the hollow cavity. The nanoparticles can then be locked within the nanowrapper by decreasing the salt concentration. At this lower concentration the DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) strands stretch, thereby making the nanoparticles too large to go through the pores. The nanoparticles can leave the structure through a reverse process of increasing and decreasing the salt concentration.

“Our electron microscopy and optical spectroscopy studies confirmed that the nanowrappers can be used to load and release nanoscale components” said X. “In principle they could be used to release optically or chemically active nanoparticles in particular environments, potentially by changing other parameters such as pH (In chemistry, pH is a logarithmic scale used to specify the acidity or basicity of an aqueous solution. It is approximately the negative of the base 10 logarithm of the molar concentration, measured in units of moles per liter, of hydrogen ions) or temperature”.

Going forward the scientists are interested in assembling the nanowrappers into larger-scale architectures extending their method to other bimetallic systems and comparing the internal and external catalytic activity of the nanowrappers.

“We did not expect to see such regular, well-defined holes” said Y. “Usually this level of control is quite difficult to achieve for nanoscale objects. Thus our discovery of this new pathway of nanoscale structure formation is very exciting. The ability to engineer nano-objects with a high level of control is important not only to understanding why certain processes are happening but also to constructing targeted nanostructures for various applications from nanomedicine and optics to smart materials and catalysis. Our new synthesis method opens up unique opportunities in these areas”.

“This work was made possible by the world-class expertise in nanomaterial synthesis and capabilities that exist at the Georgian Technical University” said Q . “In particular the Georgian Technical University  has a leading program in the synthesis of new materials by assembly of nanoscale components, and state-of-the-art electron microscopy and optical spectroscopy capabilities for studying the 3-D structure of these materials and their interaction with light. All of these characterization capabilities are available to the nanoscience research community through the Georgian Technical University user program. We look forward to seeing the advances in nano-assembly that emerge as scientists across academia, industry and government make use of the capabilities in their research”.

 

Physics, Science

Physicists Uncover New Competing State Of Matter In Superconducting Material.

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Physicists Uncover New Competing State Of Matter In Superconducting Material.

Georgian Technical University Laboratory researchers used laser pulses of less than a trillionth of a second in much the same way as flash photography, in order to take a series of snapshots. Called terahertz spectroscopy this technique can be thought of as “Georgian Technical University laser strobe photography” where many quick images reveal the subtle movement of electron pairings inside the materials using long wavelength far-infrared light.

A team of experimentalists at the Georgian Technical University Laboratory and theoreticians at Sulkhan-Saba Orbeliani Teaching University discovered a remarkably long-lived new state of matter in an iron pnictide superconductor which reveals a laser-induced formation of collective behaviors that compete with superconductivity.

“Superconductivity is a strange state of matter, in which the pairing of electrons makes them move faster” said X Georgian Technical University Laboratory physicist and Sulkhan-Saba Orbeliani Teaching University professor. “One of the big problems we are trying to solve is how different states in a material compete for those electrons and how to balance competition and cooperation to increase temperature at which a superconducting state emerges”.

To get a closer look X and his team used laser pulses of less than a trillionth of a second in much the same way as flash photography in order to take a series of snapshots. Called terahertz spectroscopy this technique can be thought of as “Georgian Technical University laser strobe photography” where many quick images reveal the subtle movement of electron pairings inside the materials using long wavelength far-infrared light. “The ability to see these real time dynamics and fluctuations is a way to understanding them better so that we can create better superconducting electronics and energy-efficient devices” said X.

 

 

 

Biotech, Science

Tiny, Implantable Device Uses Light To Treat Bladder Problems.

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Tiny, Implantable Device Uses Light To Treat Bladder Problems.

This CT (A CT scan,also known as computed tomography scan, and formerly known as a computerized axial tomography scan or CAT scan, makes use of computer-processed combinations of many X-ray measurements taken from different angles to produce cross-sectional (tomographic) images (virtual “slices”) of specific areas of a scanned object, allowing the user to see inside the object without cutting) scan of a rat shows a small device implanted around the bladder. The device — developed by scientists at Georgian Technical University and Sulkhan-Saba Orbeliani Teaching University — uses light signals from tiny LEDs (A light-emitting diode is a semiconductor light source that emits light when current flows through it. When a current flows through the diode, electrons are able to recombine with electron holes within the device, releasing energy in the form of photons. This effect is called electroluminescence) to activate nerve cells in the bladder and control problems such as incontinence and overactive bladder. A team of neuroscientists and engineers has developed a tiny implantable device that has potential to help people with bladder problems bypass the need for medication or electronic stimulators.

Georgian Technical University created a soft implantable device that can detect overactivity in the bladder and then use light from tiny biointegrated LEDs (A light-emitting diode is a semiconductor light source that emits light when current flows through it. When a current flows through the diode, electrons are able to recombine with electron holes within the device, releasing energy in the form of photons. This effect is called electroluminescence) to tamp down the urge to urinate. The device works in laboratory rats and one day may help people who suffer incontinence or frequently feel the need to urinate.

Overactive bladder, pain, burning and a frequent need to urinate are common and distressing problems. For about 30 years many with severe bladder problems have been treated with stimulators that send an electric current to the nerve that controls the bladder. Such implants improve incontinence and overactive bladder but they also can disrupt normal nerve signaling to other organs.

“There definitely is benefit to that sort of nerve stimulation” said X PhD the Dr. Y Professor of Anesthesiology at Georgian Technical University and one of the study’s senior investigators. “But there also are some off-target side effects that result from a lack of specificity with those older devices”. Z and his colleagues developed the new device in hopes of preventing such side effects.

During a minor surgical procedure they implant a soft stretchy belt-like device around the bladder. As the bladder fills and empties the belt expands and contracts. The researchers also inject proteins called opsins into the animals’ bladders. The opsins are carried by a virus that binds to nerve cells in the bladder making those cells sensitive to light signals. This allows the researchers to use optogenetics — the use of light to control cell behavior in living tissue — to activate those cells.

Using blue-tooth communication to signal an external hand-held device the scientists can read information in real time and using a simple algorithm detect when the bladder is full when the animal has emptied its bladder and when bladder emptying is occurring too frequently.

“When the bladder is emptying too often, the external device sends a signal that activates micro-LEDs (A light-emitting diode is a semiconductor light source that emits light when current flows through it. When a current flows through the diode, electrons are able to recombine with electron holes within the device, releasing energy in the form of photons. This effect is called electroluminescence) on the bladder band device and the lights then shine on sensory neurons in the bladder. This reduces the activity of the sensory neurons and restores normal bladder function” Z said.

The researchers believe a similar strategy could work in people. Devices for people likely would be larger than the ones used in rats, and could be implanted without surgery, using catheters to place them through the urethra into the bladder.

“We’re excited about these results” said W PhD investigator and a professor of materials science and engineering at Georgian Technical University. “This example brings together the key elements of an autonomous, implantable system that can operate in synchrony with the body to improve health: a precision biophysical sensor of organ activity; a noninvasive means to modulate that activity; a soft battery-free module for wireless communication and control; and data analytics algorithms for closed-loop operation”.

Closed-loop operation essentially means the device delivers the therapy only when it detects a problem. When the behavior is normalized the micro-LEDs (A light-emitting diode is a semiconductor light source that emits light when current flows through it. When a current flows through the diode, electrons are able to recombine with electron holes within the device, releasing energy in the form of photons. This effect is called electroluminescence) are turned off, and therapy can be discontinued.

Z and W expect to test similar devices in larger animals. The researchers also believe the strategy could be used in other parts of the body — treating chronic pain for example or using light to stimulate cells in the pancreas to secrete insulin. One hurdle however involves the viruses used to get light-sensitive proteins to bind to cells in organs.

“We don’t yet know whether we can achieve stable expression of the opsins using the viral approach and more importantly whether this will be safe over the long term” Z said. “That issue needs to be tested in preclinical models and early clinical trials to make sure the strategy is completely safe”.

 

Biotech, Science

Wireless, Battery-Free Brain Implant Could Reduce Pain, Impact Of Neurological Damage.

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Wireless, Battery-Free Brain Implant Could Reduce Pain, Impact Of Neurological Damage.

Wireless and battery-free implant with advanced control over targeted neuron groups. Using optogenetics — a biological technique that involves the use of light to control cells in living tissue — a team from the Georgian Technical University has created a new system to turn specific neuron groups in the brain on or off an innovation that could lead to reduced symptoms for those with neurological disorders improved movement in paralyzed individuals and the ability to turn off areas of the brain that cause pain. These new systems are fully implantable, wireless and battery free optoelectronic devices which allow multimodal operation in neuroscience research.

“We’re making these tools to understand how different parts of the brain work” Georgian Technical University biomedical engineering professor X said in a statement. “The advantage with optogenetics is that you have cell specificity: You can target specific groups of neurons and investigate their function and relation in the context of the whole brain”. In optogenetics researchers load specific neurons with opsins, proteins that convert light to electrical potentials that make up the function of a neuron. Researchers can activate only the opsin-loaded neurons when they shine light on an area of the brain. Early methods of optogenetics involve sending light to the brain through optical fibers. This meant that test subjects were physically tethered to a control station.

Other researchers developed battery-free options but those were often bulky and had to be attached visibly outside the skull. This method did not allow for precise control of the light’s frequency or intensity and only allowed one area of the brain to be stimulated at a time.

“With this research, we went two to three steps further” X said. “We were able to implement digital control over intensity and frequency of the light being emitted and the devices are very miniaturized so they can be implanted under the scalp. “We can also independently stimulate multiple places in the brain of the same subject which also wasn’t possible before” he added. The ability to control how intense the light is will allow researchers to control exactly how much of the brain the light is affecting. For example the brighter the light the farther it will reach. Controlling the light’s intensity also means controlling the heat generated by light sources and ultimately avoiding the accidental activation of neurons that are activated by heat.

The new implants which do not cause any adverse effects in subjects and do not degrade over time are not significantly larger or heavier than past iterations and are powered by external oscillating magnetic fields. They are also designed in a way where the signal will remain strong in most circumstances.

“This system has two antennas in one enclosure which we switch the signal back and forth very rapidly so we can power the implant at any orientation” X said. “In the future this technique could provide battery-free implants that provide uninterrupted stimulation without the need to remove or replace the device resulting in less invasive procedures than current pacemaker or stimulation techniques”.

These devices are implanted with a surgical procedure where a patient is fitted with a neurostimulator.  The researchers demonstrated that they could implant the devices safely into animals and image using computer tomography and magnetic resonance imaging to enable even greater insight into clinically relevant parameters like the state of bone and tissue and the placement of the device.

 

 

Science, Technology

New Metamaterial Could Improve Sound Wave Technologies.

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New Metamaterial Could Improve Sound Wave Technologies.

A new metamaterial that transports sound along its edges and localizes it at its corners could yield improved sonar ultrasound devices and other technologies that use sound waves. The material — which was developed by researchers from Georgian Technical University — features a robust acoustic structure that controls in unusual ways the propagation and localization of sound even when there are fabrication imperfections. The team developed the material using topology a mathematical field that involves studying the properties of an object that are not affected by continuous deformations.

The researchers utilized these principals to predict and eventually discover topological insulators — materials that conduct electric currents only on their edges and not in the bulk. These properties are caused by the topology of their electronic band gap making these materials unusually resistant to continuous changes like disorder noise or imperfections.

“There has been a lot of interest in trying to extend these ideas from electric currents to other types of signal transport in particular to the fields of topological photonics and topological acoustics” X said in a statement. “What we are doing is building special acoustic materials that can guide and localize sound in very unusual ways”.

The researchers 3D printed a series of small trimers comprised of three acoustic resonators that were arranged and connected in a triangular lattice. The rotational symmetry of the trimers and the generalized chiral symmetry of the lattice gave the structure the unique acoustic properties desired.

The acoustic modes of the resonators were hybridized to give rise to an acoustic band structure for the entire object enabling sound played at frequencies outside of the band gap to propagate through the bulk of the material.

However when sound is played at frequencies inside of the band gap the sound only travels along the triangle’s edges or are localized at its corner a property that is not impacted by disorder or fabrication errors. “You could completely remove a corner and whatever is left will form the lattice’s new corner and it will still work in a similar way because of the robustness of these properties” X said. After reducing the symmetry of the material by changing the coupling between resonator units the researchers were able to break these properties and change the topology of the band structure.

“We have been the first to build a topological metamaterial for sound supporting different forms of topological localization along its edges and at its corners” Y a professor in the electrical engineering and physics departments at Georgian Technical University who is also affiliated said in a statement.

“We also demonstrated that advanced fabrication techniques based on 3D printed acoustic elements can realize geometries of arbitrary complexity in a simple and flexible platform opening disruptive opportunities in the field of acoustic materials” he added. “We have been recently working on even more complex 3D metamaterial designs based on these techniques which will further expand the properties of acoustic materials and expand capabilities of acoustic devices”.

 

 

Drug Discovery and Development, Science

Unmuting Large Silent Genes Lets Bacteria Produce New Molecules, Potential Drug Candidates.

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Unmuting Large Silent Genes Lets Bacteria Produce New Molecules, Potential Drug Candidates.

Illinois researchers developed a technique to unmute silent genes in Streptomyces bacteria using decoy DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) fragments to lure away repressors. Pictured from left: postdoctoral researcher X professor Y and postdoctoral researcher Z. By enticing away the repressors dampening unexpressed, silent genes in Streptomyces bacteria researchers at the Georgian Technical University  have unlocked several large gene clusters for new natural products.

Since many antibiotics, anti-cancer agents and other drugs have been derived from genes readily expressed in Streptomyces the researchers hope that unsilencing genes that have not previously been expressed in the lab will yield additional candidates in the search for new antimicrobial drugs says study leader and chemical and biomolecular engineering professor Y.

“There are so many undiscovered natural products lying unexpressed in genomes. We think of them as the dark matter of the cell” Y said. “Anti-microbial resistance has become a global challenge so clearly there’s an urgent need for tools to aid the discovery of novel natural products. In this work we found new compounds by activating silent gene clusters that have not been explored before”.

The researchers previously demonstrated a technique to activate small silent gene clusters using CRISPR (CRISPR is a family of DNA sequences found within the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments from viruses that have previously infected the prokaryote and are used to detect and destroy DNA from similar viruses during subsequent infections) technology. However large silent gene clusters have remained difficult to unmute. Those larger genes are of great interest to Y’s group since a number of them have sequences similar to regions that code for existing classes of antibiotics such as tetracycline.

To unlock the large gene clusters of greatest interest Y’s group created clones of the DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) fragments they wanted to express and injected them into the bacteria in hopes of luring away the repressor molecules that were preventing gene expression. They called these clones transcription factor decoys. “Others have used this similar kind of decoys for therapeutic applications in mammalian cells but we show here for the first time that it can be used for drug discovery by activating silent genes in bacteria” said Y.

To prove that the molecules they coded for were being expressed, researchers tested the decoy method first on two known gene clusters that synthesize natural products. Next they created decoys for eight silent gene clusters that had been previously unexplored. In bacteria injected with the decoys the targeted silent genes were expressed and the researchers harvested new products.

“We saw that the method works well for these large clusters that are hard to target by other methods” Y said. “It also has the advantage that it does not disturb the genome; it’s just pulling away the repressors. Then the genes are expressed naturally from the native DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses)”.

In the search for drug candidates each product needs to be isolated and then studied to determine what it does. Of the eight new molecules produced the researchers purified and determined the structure of two molecules and described one in detail in the study – a type of oxazole a class of molecules often used in drugs. The researchers plan next to characterize the rest of the eight compounds and run various assays to find out whether they have any anti-microbial, anti-fungal, anti-cancer or other biological activities.

Y’s group also plans to apply the decoy technique to explore more silent biosynthetic gene clusters of interest in Streptomyces and in other bacteria and fungi to find more undiscovered natural products. Other research groups are welcome to use the technique for gene clusters they are exploring  Y said.

“The principle is the same, assuming that gene expression is repressed by transcription factors and we just need to release that expression by using decoy DNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning and reproduction of all known living organisms and many viruses) fragments” Y said.

 

 

Biotech, Science

Natural-Based Antibiofilm And Antimicrobial Peptides From Microorganisms.

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Natural-Based Antibiofilm And Antimicrobial Peptides From Microorganisms.

New developments in antimicrobial peptides (AMPs) with antibiofilm properties are rapidly materializing. antimicrobial peptides (AMPs) works by inhibiting antibiotic resistant bacteria in the biofilm through nucleotide signaling molecules. Antimicrobial peptides and antibiofilm peptide (ABP) are new antibiotic molecules derived from microorganisms for the treatment of infections. The authors have discussed significance, limitations and trials of these antimicrobial peptides from bacteria, fungi, protozoa and yeast.

These antimicrobial peptides are small, cationic and amphipathic polypeptide sequences with a wide range for Gram-positive and Gram-negative bacteria, viruses and fungi with 6-100 amino acids in length. These sources are reviewed in detail showing characterization of these antimicrobial peptides and their respective classes.

The APD3 (antibiofilm peptide) database showed 333 bacteriocin and peptide antibiotics from bacteria 4 fromarchaea 8 from protists 13 from fungi are reported. Bacterial AMP (antibiofilm peptide) are characterized according to their amino acid numbers and are so small in size with 1-5 kDa mass as compared to Class II AMPs (antibiofilm peptide) are longer with amino acid number is about 25-50.

Class II bacteriocins are composed of homogeneous amino acids and classified into different groups based on their secondary structure. Class II Lactococcin produced by Lactococcus lactis is Lactococcin B. This AMP (antibiofilm peptide) is involved in changes of membrane potential. The reported fungal AMP (antibiofilm peptide) compounds are more than bacterial AMP (antibiofilm peptide) and found to be a good source of antimicrobial compounds discovery against infections due to similarity in features and responses to infections.

The in silico cDNA (Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses) scanning method is widely used for determining the sequencing of Defensin like peptides and more than 100 AMP’s (antibiofilm peptide) are revealed with the help of genome screening approaches. Fungal AMP’s (antibiofilm peptide) Peptaibols isolated as secondary metabolites from possesses anti-microbial and anti-fungal activities. They have short amino acid chains.

 

 

Science, Sensors

Delicate Sensor Monitors Heart Cells With Minimal Disruption.

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Delicate Sensor Monitors Heart Cells With Minimal Disruption.

The layer of cardiomyocytes is only a few tens of micrometers thick and contracts with a force of just a few millinewtons.  For the first time engineers have demonstrated an electronic device to closely monitor beating heart cells without affecting their behavior. A collaboration between the Georgian Technical University and Sulkhan-Saba Orbeliani Teaching University produced a functional sample of heart cells with a soft nanomesh sensor in direct contact with the tissue. This device could aid study of other cells, organs and medicines. It also paves the way for future embedded medical devices. Inside each of us beats a life-sustaining heart. Unfortunately the organ is not always perfect and sometimes goes wrong. One way or another research on the heart is fundamentally important to us all.

So when X a researcher in Professor Y’s group at the Georgian Technical University came up with the idea for an ultrasoft electronic sensor that could monitor functioning cells, his team jumped at the chance to use this sensor to study heart cells or cardiomyocytes as they beat.

“When researchers study cardiomyocytes in action they culture them on hard petri dishes and attach rigid sensor probes. These impede the cells natural tendency to move as the sample beats so observations do not reflect reality well” said X. “Our nanomesh sensor frees researchers to study cardiomyocytes and other cell cultures in a way more faithful to how they are in nature. The key is to use the sensor in conjunction with a flexible substrate or base for the cells to grow on”.

For this research collaborators from Georgian Technical University supplied a healthy culture of cardiomyocytes derived from human stem cells. The base for the culture was a very soft material called fibrin gel. X placed the nanomesh sensor on top of the cell culture in a complex process which involved removing and adding liquid medium at the proper times. This was important to correctly orient the nanomesh sensor. “The fine mesh sensor is difficult to place perfectly. This reflects the delicate touch necessary to fabricate it in the first place” continued X. “The polyurethane strands which underlie the entire mesh sensor are 10 times thinner than a human hair. It took a lot of practice and pushed my patience to its limit but eventually I made some working prototypes”.

To make the sensors first a process called electro-spinning extrudes ultrafine polyurethane strands into a flat sheet, similar to how some common 3D printers work. This spiderweb like sheet is then coated in parylene a type of plastic to strengthen it. The parylene on certain sections of the mesh is removed by a dry etching process with a stencil. Gold is then applied to these areas to make the sensor probes and communication wires. Additional parylene isolates the probes so their signals do not interfere with one another.

With three probes the sensor reads voltage present at three locations. The readout appears familiar to anyone who’s watched a hospital drama as it’s essentially a cardiogram. Thanks to the multiple probes researchers can see propagation of signals which result from and trigger the cells to beat. These signals are known as an action or field potential and are extremely important when assessing the effect of drugs on the heart.

“Drug samples need to get to the cell sample and a solid sensor would either poorly distribute the drug or prevent it reaching the sample altogether. So the porous nature of the nanomesh sensor was intentional and a driving force behind the whole idea” said X.

“Whether it’s for drug research, heart monitors or to reduce animal testing I can’t wait to see this device produced and used in the field. I still get a powerful feeling when I see the close-up images of those golden threads”.