#CRISPR Brings Precise Control to Gene expression Researchers have demonstrated the exceptional specificity of a new way to switch sequences of the human genome on
or off without editing the underlying genetic code. Originally discovered as an antiviral system in bacteria,
CRISPR/Cas9 is one of the hottest topics in genetic research today. By engineering a version of that system,
researchers can both edit DNA sequences and control which genes are used. Previous studies, however, showed that editing human DNA sequences with the system is not always as precise as researchers would like.
Those results raised concerns about the use of CRISPR technology in studying human diseases. As a potential solution
some researchers added more versatility to the system by using CRISPR to target portions of DNA that control
which genes are active. But instead of using the genetic cutting tool Cas9 that is often employed, they inactivated the cutting function of Cas9 and attached proteins that control the packaging of the genome.
By unraveling or tightly bundling these regions of the genome, they could effectively turn them on and off.
While the technique had been shown to work well, whether or not it had off-target effects had not been investigated.
Now, a team of researchers from Duke university have shown that these gene-controlling methods are capable of the high degree of precision required for basic science and medical research.
The study appears in Nature Methods. he primary advantage of CRISPR over previous technologies is the ability to use a genetic scalpel rather than a sledgehammer,
associate professor of biomedical engineering at Duke university. any labs across the world are using these tools on the assumption that theye getting specific effects,
These experiments show exceptional specificity, demonstrating that the technology is capable of targeting single sequences of the genome.
The power to control the genome switches would be especially important for studying and potentially treating human diseases such as cancer,
cardiovascular disease, neurodegenerative conditions and diabetes, which can be driven by mutations in control regions of the genome.
The hope is that overriding one of these switches could uncover and fix the root causes of many diseases.
It could also help researchers understand and change how different people respond to drugs. But only if the CRISPR technique is specific enough.
Soon after CRISPR was described first for editing human genes, several papers revealed that the technique can sometimes have off-target effects.
This presents problems for gene therapy treatments and fundamental science projects, where researchers want to alter the function of specific genes without causing unintended side effects An alternative strategy was developed to switch on
assistant professor of biostatistics and bioinformatics at Duke. inding a change in sequence or gene activity is relatively straightforward
if youe focusing on one concentrated area in the genome. But looking at how turning off one enhancer switch affects the activity
and structure of the whole genome requires more specialized techniques. Gersbach turned to Reddy and colleague Gregory Crawford
who all work together in adjacent laboratories and offices in Duke Center for Genomic and Computational biology, for help with these more specialized techniques.
Reddy has focused his career on investigating how gene switches work across the human genome, how those switches differ between individuals and the implications of these insights for human traits and diseases.
Crawford, associate professor of pediatrics, has spent more than a decade developing techniques to identify control regions across the genome
and how they vary between cell types, during development or in response to drug treatment. urrent methods for controlling gene switches,
change the activity of many switches across the genome simultaneously, creating thousands of off-target effects,
It fell to Pratiksha Thakore, a Phd student in Gersbach lab, to integrate the expertise of all three laboratories for studying the specificity of CRISPR in controlling these switches.
it provides a blueprint for researchers to assess these effects. y integrating genomics and genome engineering,
we have developed a method to comprehensively interrogate how this genetic silencing system works and also suggested ways the technology can be used in the future,
#Collaboration identifies critical macular-development gene Researchers at the University of Iowa Stephen A. Wynn Institute for Vision Research announced the discovery of a gene that controls the development of the human macula.
The discovery was published electronically in the journal Ophthalmology. his is the culmination of more than 20 years of work,
. a retina specialist affiliated with Cedars-Sinai Board of Governors Regenerative medicine Institute in Los angeles. Small, the study lead author,
first mapped the gene causing North carolina macular dystrophy on chromosome 6 in 1992. The current findings ultimately required an international team of 20 investigators using data from the Human genome Project
and an elaborate computer analysis to identify the actual mutations in INTERGENIC DNA near the PDRM13 gene. ndividuals with this disease have normal eyes except that they fail to form maculas,
Small says. nderstanding how this gene works may help us treat many macular diseases more effectively in the future. cientists already know how to create new retinal cells from a patient skin,
says Edwin Stone, M d.,Ph d.,director of the Wynn Institute for Vision Research and a coauthor of the study. his new finding will help us learn how nature builds a macula
Ltd. s a person who knows firsthand what it is like to lose vision from a rare, inherited eye disease,
and I feel that the prospect of finding a cure is possible and probable in the short term
and certain in the long term. s a public research university working to solve some of society greatest health and medical challenges,
says Jean Robillard, M d.,interim president of the University of Iowa and vice president for medical affairs, University of Iowa Health care s
which is the leading cause of serious long-term disability in adults. The five-year study, performed in an animal model,
the study senior author and a professor and vice chair for research and programs in the UCLA department of neurology. he brain has limited a capacity for recovery after stroke,
Carmichael said. ost stroke patients get better after their initial stroke, but few fully recover.
or off by GDF10 in brain cells after a stroke and compared the cellsrna to RNA in comparable cells during brain development and normal learning,
and to RNA in the brain cells of people with other diseases. They found that GDF10 regulates a unique collection of molecules that improves recovery after stroke.
is central to most electric power plants, heating and cooling systems, and desalination plants. Now, for the first time, researchers at MIT have found a way to control this process, literally with the flick of an electrical switch.
Researchers found that sections of metal can be made to either promote bubbling (the two rectangles at the edges)
or to inhibit bubbling (center rectangles), simply by switching the polarity of voltages applied to the metal.
Image courtesy of the researchersthe system which could improve the efficiency of electric power generation and other processes, is described in a paper by Department of Mechanical engineering Professor Evelyn Wang, graduate student Jeremy Cho,
and recent graduate Jordan Mizerak 4, published in the journal Nature Communications. This degree of control over the boiling process, independent of temperature, Wang says,
has not previously been demonstrated despite the ubiquity of boiling in industrial processes. Other systems have been developed to control boiling using electric fields,
but these have required special fluids rather than water, and a thousandfold higher voltages, making them economically impractical for most uses.
The new feat was accomplished by adding surfactants to water essentially creating a soapy liquid. The surfactant molecules
or repelled by, a metal surface by changing the polarity of the voltage applied to the metal.
which rely on the creation of precise kinds of nanoscale textures on the surface, this system makes use of the tiny irregularities that naturally exist on a metal surface
in turn, allows control over the rate of heat transfer between the metal and the liquid.
That could make it possible to make more efficient boilers for powerplants or other applications, since present designs require a substantial safety margin to avoid the possibility of hot spots that could seriously damage the equipment.
While most such power plants operate at a steady rate most of the time being able to control the heat transfer rates dynamically could improve their efficiency
Similarly, liquid cooling for high-performance electronics also could be made more efficient by being able to control the rate of bubbling to prevent overheating in hotspots,
he says. aving a boiler that can respond to quick changescould provide extra flexibility to the electric grid,
Wang says this work has demonstrated hat you can actively modify the rate of nucleation. It has not been shown previously that this is possible. ower plant operators are rightly conservative about making changes,
But don think there are any huge barriersto building such a demonstration he says. n theory,
says Satish Kandlikar, a professor of mechanical engineering at the Rochester Institute of technology, who was involved not in this research. uch control strategies will dramatically alter the heat transfer paradigm in many applications,
especially in the electronics cooling industry to cool hot spots. Such strategies can be applied effectively through simple electric controls using the new technology. g
#New company to produce water-disinfecting tablets invented at UVA A new University of Virginia-inspired public benefit company with a global health mission,
and Health Conference, being held this week at the University of North carolina School of Global Public health.
The Madidrop tablet which will cost between $5 and $10, can provide clean water for up to six months.
The technology transfer company will produce ceramic water disinfection tablets called adidropsfor people in developing countries who have poor access to clean drinking water.
The Madidrop tablet, which uses silver to disinfect water, was developed and extensively tested by UVA scientists and students.
It is inexpensive to produce and can repeatedly disinfect water for up to six months by simply resting in a 10-liter household water storage container. e wanted to maximize production and distribution of Madidrop,
not to maximize profits. ames Smith and Rekha Singh, a research scientist in Smith lab, demonstrate use of the Madidrop tablet.
UVA maintains ownership of intellectual property rights for Madidrop and is exclusively licensing the technology to Madidrop PBC.
The University is one of the primary shareholders in the company, and used a Virginia Innovation Grant as seed money to move the technology beyond the lab and into the marketplace.
The National Science Foundation Innovation Corps program helped UVA organizers define their product idea for the marketplace.
000 to 200,000 Madidrop tablets in its first year, for sale primarily to nongovernmental aid organizations such as the U s. Agency for International Development, the International Rescue Committee, Catholic Relief Services
Those entities then would distribute the tablets to developing countries as needed, particularly during times of crises such as after a natural disaster.
The tablets also would be available in the United states. Madidrop PBC expects to eventually build capacity to produce 1 million to 2 million Madidrops per year.
The company intends to explore domestic applications as well. he Charlottesville factory will be a clean production facility with a simple production process
employing just a few workers in the beginning, Smith said. e plan to keep costs down so we can make Madidrop affordable in developing countries where the need is greatest. he company is starting with seven employees,
and will ramp up to about a dozen employees next year. Smith expects Madidrop tablets to cost less than $10 each,
and possibly as low as $5 each. With an effective use life of about six months per tablet, this is significantly cheaper than single-use chemical water purifying tablets,
which cost $50 to $100 for a six-month supply. According to Smith Madidrop tablets are inexpensive to produce,
are durable, reusable and easy to package, transport and ship. Unlike small chemical tablets that dissolve in water and leave a chlorine aftertaste, Madidrop is made of a continuously reusable ceramic that is simply placed in a water vessel,
such as a bucket, and left there for several hours or overnight. Silver ions are released gradually from the tablet,
killing pathogens by penetrating cell membranes and disrupting cell division. Extensive testing at UVA labs show that the tablet causes better than a 99.99 percent reduction in such infectious waterborne bacteria as Vibrio cholera
Escherichia coli and other coliform bacteria. The Madidrop also is effective at reducing the infectivity of protozoan pathogens including Giardia lamblia and Cryptosporidium parvum, all of
which cause severe diarrhea, vomiting, dehydration and potential long-term growth and cognition deficiencies. These pathogens are particularly devastating to children and people with AIDS.
Smith said that most of the revenue from sales of Madidrop initially will be fed back into the company to fuel production expansion.
Public service-minded investors will become shareholders and eventually make small profits. Madidrop PBC will provide profit-sharing for employees
and the highest-paid employee will never make more than 15 times the salary of the lowest-paid employee.
The company has raised an initial round of funding from private investors t a different mindset,
a nonprofit/traditional company hybrid profit-making for the public good, Smith said. e are actively raising additional capital to help us bring this innovative public health product to people in need around the world. adidrop PBC administrative office is located on Allied Street in Charlottesville
and the production facility is on Avon Street o
#Deep-sea bacteria could help neutralize greenhouse gas, researchers find A type of bacteria plucked from the bottom of the ocean could be put to work neutralizing large amounts of industrial carbon dioxide in the Earth atmosphere,
a group of University of Florida researchers has found. Carbon dioxide, a major contributor to the buildup of atmospheric greenhouse gases, can be captured
and neutralized in a process known as sequestration. Most atmospheric carbon dioxide is produced from fossil fuel combustion, a waste known as flue gas.
But converting the carbon dioxide into a harmless compound requires a durable heat-tolerant enzyme. That where the bacterium studied by UF Health researchers comes into play.
The bacterium Thiomicrospira crunogena produces carbonic anhydrase, an enzyme that helps remove carbon dioxide in organisms.
So what makes the deep-sea bacterium so attractive? It lives near hydrothermal vents, so the enzyme it produces is accustomed to high temperatures.
That exactly what needed for the enzyme to work during the process of reducing industrial carbon dioxide,
said Robert Mckenna, Ph d.,a professor of biochemistry and molecular biology in the UF College of Medicine,
a part of UF Health. his little critter has evolved to deal with those extreme temperature and pressure problems.
It has adapted already to some of the conditions it would face in an industrial setting,
he said. The findings by the Mckenna group, which included graduate research assistants Brian Mahon and Avni Bhatt,
were published recently in the journals Acta Crystallographica D: Biological Crystallography and Chemical engineering Science. The chemistry of sequestering works this way:
The enzyme, carbonic anhydrase, catalyzes a chemical reaction between carbon dioxide and water. The carbon dioxide interacts with the enzyme,
converting the greenhouse gas into bicarbonate. The bicarbonate can then be processed further into products such as baking soda and chalk.
In an industrial setting, the UF researchers believe the carbonic anhydrase could be captured this way:
The carbonic anhydrase would be immobilized with solvent inside a reactor vessel that serves as a large purification column.
Flue gas would be passed through the solvent, with the carbonic anhydrase converting the carbon dioxide into bicarbonate.
Neutralizing industrial quantities of carbon dioxide can require a significant amount of carbonic anhydrase, so Mckenna group found a way to produce the enzyme without repeatedly harvesting it from the sea floor.
they want to study ways to increase the enzyme stability and longevity, which are important issues to be addressed before the enzyme could be put into widespread industrial use.
#Bioengineers cut in half time needed to make high-tech flexible sensors Bioengineers at the University of California,
San diego, have developed a method that cuts down by half the time needed to make high-tech flexible sensors for medical applications.
The advance brings the sensors, which can be used to monitor vital signs and brain activity, one step closer to mass-market manufacturing.
The new fabrication process will allow bioengineers to broaden the reach of their research to more clinical settings.
It also makes it possible to manufacture the sensors with a process similar to the printing press
a bioengineering professor at the Jacobs School of engineering at UC San diego. Researchers describe their work in the journal Sensors. clinical need is
Coleman team at UC San diego has been working in medical settings for four years. Their sensors have been used to monitor premature babies, pregnant women,
patients in Intensive care units and patients suffering from sleep disorders. Coleman and colleagues quickly found out that nurses wanted the sensors to come in a peel-and-stick form,
like a medical-grade Band aid. The medium on which the sensors were placed also needed to be approved FDA.
The sensorsoriginal fabrication process involved 10 stepsive of which had to take place in a clean room.
Also, the steps to remove the sensors from the silicon wafer theye built on alone took anywhere from 10 to 20 minutes.
And the sensors remained fragile and susceptible to rips and tears. But what if you could use the adhesive properties of a Band aid-like medium to help peel off the sensors from the silicon wafer easily and quickly?
Wouldn that make the process much simplernd faster? That was the question that Dae Kang,
a Jacobs School Ph d. student in Coleman research group, set out to answer. The result of his efforts is a process that comprises only six stepshree of them in the clean room.
made of a silicon-like material called an elastomer, to easily remove the sensors, made of gold and chromium, from the silicon wafer.
This was tricky work. The coating had be sticky enough to allow researchers to build the sensors in the first place
but loose enough to allow them to peel off the wafer. t a Goldilocks problem, Coleman said.
The new process doesn require any chemical solvents. That means the sensors can be peeled off with any kind of adhesive, from scotch tape to a lint roller,
as researchers demonstrated in the study. Coleman team also showed that the sensors could be fabricated on a curved,
flexible film typically used to manufacture flexible printed circuits and the outside layer of spacesuits. Researchers were able to easily peel off the sensors from the curved film without compromising their functioning.
In order to make the sensors more like peel off stickers researchers essentially had to build the sensors upside down
so that their functioning part would be exposed after they were removed from the wafer. This was key to allow for easy processing with a single peel off step.
Researchers also demonstrated that the sensors they built with the new fabrication process were functional.
They placed a sensor on a subject forehead and hooked it up to an electroencephalography machine.
The sensors were able to detect a special brain signal present only when the subject eyes were closed classic electroencephalogram testing procedure.
The researchers also demonstrated that these sensors are able to detect other electrical rhythms of the body
such as the heart electrical activity detected during an electrocardiogram or EKG e
#Bacterial hole puncher could be new broad-spectrum antibiotic Bacteria have many methods of adapting to resist antibiotics,
but a new class of spiral polypeptides developed at the University of Illinois targets one thing no bacterium can live without:
an outer membrane. The polypeptides, which are short protein chains, act as bacterial hole-punchers, perforating the bacterial membrane until the cell falls apart.
The antimicrobial agents are dressed for their mission in a positively charged shell that lets them travel in body fluids,
protected from interacting with other proteins, and also attracts them to bacterial membranes. Led by U. of I. materials science and engineering professor Jianjun Cheng,
the researchers published their findings in the Proceedings of the National Academy of Sciences. hen you have an infection,
it can be very difficult for a doctor to know which bacteria is infecting you,
said postdoctoral researcher Menghua Xiong, a co-first author of the paper. any antimicrobial agents can only cure one class of bacteria.
A doctor may try one class, and if that doesn work, try another class. We need more broad-spectrum antimicrobial agents.
The new antimicrobial polypeptides are designed specially to fold into a rigid spiral resulting in a rodlike structure,
Such structures have been investigated for various medical applications but because they do not like water, they do not travel well in bodily fluids.
#Nanotechnology could spur new heart treatment for arrthymia A new nanoparticle developed by University of Michigan researchers could be the key to a targeted therapy for cardiac arrhythmia,
and can lead to heart attack and stroke. The disease affects more than four million Americans and causes over 750,000 hospitalizations and 130,000 deaths per year in the United states alone.
The new treatment uses nanotechnology to precisely target and destroy the cells within the heart that cause cardiac arrhythmia.
In studies conducted on rodents and sheep the U-M team found that the treatment successfully kills the cells that cause cardiac arrhythmia while leaving surrounding cells unharmed.
Their findings are detailed in a new paper published in the journal Science Translational Medicine.
Cardiac arrhythmia is caused by malfunctions in a certain type of heart muscle cell, which normally helps regulate the heartbeat.
Today, the disease is treated usually with drugs, which can have serious side effects. It can also be treated with a procedure called cardiac ablation that burns away the malfunctioning cells using a high-powered laser that threaded into the heart on a catheter.
The laser also damages surrounding cells which can cause artery damage and other serious problems.
The team, led by Jérôme Kalifa, M d.,Ph d.,a cardiologist and U-M Medical school assistant professor at the Center for Arrhythmia Research,
and Raoul Kopelman, a chemist, materials scientist and the Richard Smalley Distinguished Professor of Chemistry, Physics and Applied Physics, set out to target
Widely used today to treat cancer, the technique requires doctors to mark unwanted cells with a chemical that makes them sensitive to low-level red light.
The red light then destroys the marked cells while leaving surrounding tissue unharmed. he great thing about this treatment is that it precise down to the level of individual cells,
The major challenge of adapting the therapy to heart cells was developing a nanoparticle small enough to penetrate the tiny pores inside heart capillaries,
yet large enough to carry the chemical payload needed to do the job. n our cancer work,
we used nanoparticles that were about 120 nanometers in size, says Kopelman. o work inside the heart,
we needed to develop a particle that did the same job but was only 6 nanometers in size.
Incredibly tiny even by nanotechnology standards the particle had to pack in the light sensitivity chemical,
an amino acid that causes it to be absorbed only by a specific type of heart muscle cells,
The particle has eight nanoscale tentacles, offering plenty of points to attach the chemicals needed for the process.
and a research lab specialist in internal medicine. his cell-selective therapy may represent an innovative concept to overcome some of the current limitations of cardiac ablation,
The team tested a treatment that delivers the photo sensitizing chemical (made from algae) to the targeted cells by injecting nanoparticles loaded with both the chemical
and an amino acid-based peptide that causes the nanoparticles to be taken up only by the targeted cells.
The low-level light destroys only the cells that have absorbed the nanoparticles leaving the other heart cells unharmed.
The team is also working to devise a method for producing larger quantities of the nanoparticles at pharmaceutical-grade standards.
#Cell stress response and fat and obesity gene linked In one fell swoop, Cornell researchers have discovered mechanisms that control the function of a fat
and obesity gene while at the same time answering a longstanding question about how cells respond to stress.
when they have fevers. The genes express heat shock proteins which protect essential cell proteins and remove damaged proteins before they accumulate
disease and cell death. eat shock genes and their heat shock proteins are expressed highly during stress and are very critical to protect cells;
without them cells would quickly die under stress, said Shu-Bing Qian, associate professor of nutritional sciences,
and the paper senior author, along with Dr. Samie Jaffrey, professor of pharmacology at Weill Cornell Medicine.
Jun Zhou, a postdoctoral research associate in Qian lab, is the paper first author. The process of making heat shock proteins is not simple,
and it is associated also with diabetes, he said. The gene produces an FTO enzyme, which acts as a demethylase,
Many years ago, researchers observed that obese people have poor cellular stress responses. This may be because their heat shock proteins are reduced,
and accumulate during stress. he accumulation of damaged proteins disregulates the whole metabolism, said Qian. e suspect this could be one cause of obesity.
whether FTO enzymes and their effect on heat shock genes and proteins could be promoting obesityand diabetes,
#Molecular Switch Generates Calorie-Burning Brown Fat A research team led by UC San francisco scientists has identified a molecular switch capable of converting unhealthy white fat into healthy, energy-burning
Drugs that flip this switch rapidly reduced obesity and diabetes risk factors in mice fed a high fat diet.
The results suggest that drugs capable of targeting similar molecular pathways in human fat cells could one day become major tools for fighting the growing worldwide epidemics of obesity and type 2 diabetes, according to senior
investigator Shingo Kajimura, Phd, an assistant professor of cell and tissue biology in UCSF School of dentistry. He holds a joint appointment in UCSF Diabetes Center and Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research.
The research appears Oct 29 in the journal Cell Metabolism. All mammals, including humans, have two types of fat with completely opposite functions:
white, which stores energy and is linked with diabetes and obesity; and brown, which produces heat by burning energy
and is associated with leanness. Human babies are born with brown fat as a natural defense against cold.
Many obesity researchers hope to harness the energy-burning capacity of brown fat to help patients lose weight:
enhancing people baseline stores of energy-burning brown fat, known as the rowningof white fat. In the new paper, Kajimura team collaborated with the laboratory of Yasushi Ishihama, Phd, of the University of Kyoto, Japan,
to search for differences in how white and brown fat cells respond to the cold using a technique called phosphoproteomics.
which appears to be responsible for preventing white fat from burning energy for heat in cold conditions.
becoming calorie burners like their brown and beige brethren. t was quite surprising, Kajimura said. his one protein turned out to be the switch that regulates
whether fat cells burn energy or not. CK2 activity is heightened also in obese mice, the team discovered, suggesting a link between obesity
which is already in clinical trials as a cancer therapeutic; and a more precise next-generation antisense oligonucleotide (ASO) drug developed in collaboration with Isis pharmaceuticals,
and significantly increasing the amount of energy mice burned when researchers turned down the temperature in their living quarters.
The drugs also significantly reduced the negative effects of a high-fat diet in mice, including reducing weight gain and, to the researcherssurprise,
but here wee found that it could help reduce the risk of type 2 diabetes, as well.
or housing them at 17 degrees C (62.6 degrees F) each prevented more than 25 percent of this weight gain.
and whether they can be used alongside next-generation drugs that mimic the effects of cold to trigger brown fat to burn energy in humans.
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