#An easier way to manipulate malaria genes Plasmodium falciparum the parasite that causes malaria has proven notoriously resistant to scientists efforts to study its genetics.
MIT biological engineers have demonstrated now that a new genome-editing technique called CRISPR can disrupt a single parasite gene with a success rate of up to 100 percent in a matter of weeks.
and boost drug-development efforts says Jacquin Niles an associate professor of biological engineering at MIT. Even though we ve sequenced the entire genome of Plasmodium falciparum half of it still remains functionally uncharacterized.
That s about 2500 genes that if only we knew what they did we could think about novel therapeutics
The paper s lead author is Jeffrey Wagner a recent Phd recipient and current MIT postdoc in biological engineering.
Graduate student Randall Platt recent Phd recipient Stephen Goldfless and Feng Zhang the W. M. Keck Career development Assistant professor in Biomedical engineering also contributed to the research.
This occurs very rarely in the genome of the malaria parasite. You have to rely on this really inefficient process that occurs
The system includes a DNA-cutting enzyme Cas9 bound to a short RNA guide strand that is programmed to bind to a specific genome sequence telling Cas9 where to make its cut.
which P. falciparum genetics have been done in the past even 50 percent is pretty substantial. For both targets the researchers demonstrated that they could insert a gene for the protein luciferase
The general concept of using the CRISPR/Cas9 system to edit the genome of the malaria parasite is significant
because we ve struggled with the technical aspects of doing these genetic experiments says Kirk Deitsch a professor of microbiology
#A new way to model cancer Sequencing the genomes of tumor cells has revealed thousands of mutations associated with cancer.
One way to discover the role of these mutations is breed to a strain of mice that carry the genetic flaw
They have shown that a gene-editing system called CRISPR can introduce cancer-causing mutations into the livers of adult mice enabling scientists to screen these mutations much more quickly.
They are now working on ways to deliver the necessary CRISPR components to other organs allowing them to investigate mutations found in other types of cancer.
Tyler Jacks director of MIT s Koch Institute for Integrative Cancer Research and the David H. Koch Professor of Biology is the paper s senior author.
Researchers have copied this bacterial system to create gene-editing complexes that include a DNA-cutting enzyme called Cas9 bound to a short RNA guide strand that is programmed to bind to a specific genome sequence telling Cas9 where to make its Cut in some cases the researchers simply snip out
Previous studies have shown that genetically engineered mice with mutations in both of those genes will develop cancer within a few months.
which requires introducing mutations into embryonic stem cells can take more than a year and costs hundreds of thousands of dollars.
if additional mutations occur later on. To create this model the researchers had to cut out the normal version of the gene
Using CRISPR to generate tumors should allow scientists to more rapidly study how different genetic mutations interact to produce cancers as well as the effects of potential drugs on tumors with a specific genetic profile.
While this is an effective way to get genetic material to the liver it would not work for other organs of interest.
In the near term the material could also be embedded in lab-on-a-chip devices to magnetically direct the flow of cells and other biological material through a diagnostic chip s microchannels.
when it s needed such as in a microfluidic device used to test biological or chemical samples by mixing them with a variety of reagents.
MIT postdoc Seyed Mahmoudi a co-author of the paper notes that electric fields cannot penetrate into conductive fluids such as biological fluids so conventional systems wouldn t be able to manipulate them.
which have numerous applications in a variety of fields including biotechnology. He adds This work cleverly combines low-hysteresis droplet movement with low-magnetic-field-driven droplet propulsion to achieve impressive capabilities.
The biological causes of mental illnesses such as schizophrenia and bipolar disorder have mystified scientists for decades; in the last five years however understanding has accelerated dramatically driven by advances in human genomics.
Because researchers cannot study the biochemistry of the living human brain the genes that predispose people to schizophrenia
The discovery of specific genes associated with these disorders provides significant clues to their biological basis and points to possible molecular targets for novel therapies.
Stanley s new commitment is the culmination of a 25-year personal mission to discover the biology of psychiatric disorders
and begun to identify specific gene mutations and the critical underlying biological processes such as an impaired ability of neurons to communicate with each other.
We are going to illuminate the biology behind these conditions says Eric Lander founding director and president of the Broad Institute and a professor of biology at MIT.
If we know the biological causes we can begin to dispel the stigma around people battling mental illness
If you want to get at the molecular pathogenesis of these disorders you ve got to crack the genetics.
and Lander served as a member of the NIMH s Genetics Workgroup; the three had developed a mutual respect and a shared vision for
and genetics and along with Scolnick and Lander supported the collection of DNA samples from patients with the hope that the samples could someday be analyzed to find disease genes.
because the Human genome Project had not yet been completed. When Hyman left the NIMH in 2001 to become provost of Harvard he had lost almost completely hope that true progress could be made in his lifetime in elucidating the mechanisms of psychiatric illness.
Ten years ago finding the biological causes of psychiatric disorders was like trying to climb a wall with no footholds says Hyman who Is distinguished also the Service Professor of Stem Cell and Regenerative Biology at Harvard.
The Broad Institute grew from an MIT-based flagship center for the Human Genome Project
Formally founded in 2004 to fulfill the promise of the Human genome Project by facilitating collaborative biomedical research across disciplines
Celebrating its 10th anniversary this month the Broad Institute is today home to a community of more than 2000 members including physicians biologists chemists computer scientists engineers staff and representatives of many other disciplines.
Broad scientists have invented also powerful new tools that allow researchers to precisely manipulate the genome and measure the millions of complex chemical interactions within cells.
In the spirit of the Human genome Project the Broad makes its genomic data freely available to researchers around the world.
To create a comprehensive catalog of the genetic variation that underlies mental illness the researchers plan to expand their international network
They also plan to expand their sample collection efforts dramatically especially among understudied populations such as those in African nations to reveal the many as-yet-undiscovered mutations relevant to disease.
Reveal the biological pathways in which these genes act. To do so they will push technological boundaries working with new techniques that allow them to manipulate
In contrast to researchers studying cancer or diabetes researchers studying psychiatric disorders have been unable to identify animal models that correctly capture important biological aspects of the disorders
and animal models that more faithfully match both the genetic variation and the biochemical processes seen in human patients.
They plan to pioneer cutting-edge techniques such as genome editing which allows them to precisely introduce any mutations they choose.
Develop chemicals to modulate biological pathways to serve as drug leads. The researchers plan to build on the existing therapeutic efforts within the Stanley Center
and draw on the Broad s Therapeutics Platform a technological powerhouse with the capacity to create
and screen hundreds of thousands of compounds to identify molecules that can powerfully and precisely influence specific biological pathways relevant to psychiatric disorders.
We re still at the beginning of the curve of translating the emerging genetics into actionable biology but it s happening much faster than
Situated within the Broad Institute of MIT and Harvard the Stanley Center aims to exploit the most advanced technologies for human genetic analysis to study these psychiatric disorders
Pandora for example comes down to this thing that they call the music genome which contains a summary of your musical tastes.
To recommend a song all you need is the last 10 songs you listened to just to make sure you don t keep recommending the same one again and this music genome.
what songs they ll like than anything captured by Pandora s music genome. Openpds preserves all that potentially useful data but in a repository controlled by the end user not the application developer or service provider.
#Noninvasive brain control Optogenetics, a technology that allows scientists to control brain activity by shining light on neurons,
This noninvasive approach could pave the way to using optogenetics in human patients to treat epilepsy and other neurological disorders,
Led by Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT, the researchers described the protein in the June 29 issue of Nature Neuroscience.
Optogenetics, a technique developed over the past 15 years, has become a common laboratory tool for shutting off or stimulating specific types of neurons in the brain,
Most of the natural opsins now used for optogenetics respond best to blue or green light.
but had a much stronger photocurrent enough to shut down neural activity. his exemplifies how the genomic diversity of the natural world can yield powerful reagents that can be of use in biology and neuroscience,
A key advantage to this opsin is that it could enable optogenetic studies of animals with larger brains,
says Garret Stuber, an assistant professor of psychiatry and cell biology and physiology at the University of North carolina at Chapel hill. n animals with larger brains,
people have had difficulty getting behavior effects with optogenetics, and one possible reason is that not enough of the tissue is being inhibited,
This type of noninvasive approach to optogenetics could also represent a step toward developing optogenetic treatments for diseases such as epilepsy,
says Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT and one of the leaders of the research team. n short,
The new approach, described May 18 in Nature Methods, could also help neuroscientists learn more about the biological basis of brain disorders. e don really know
The researchers also plan to combine this technique with optogenetics, which enables neuronal firing to be controlled by shining light on cells engineered to express light-sensitive proteins.
Genetic information is carried normally from DNA in the nucleus to ribosomes, cellular structures where proteins are made.
Short strands of RNA called sirna bind to the MESSENGER RNA that carries this genetic information preventing it from reaching the ribosome.
With the best-performing particles, the researchers reduced gene expression by more than 50 percent, for a dose of only 0. 20 milligrams per kilogram of solution about one-hundredth of the amount required with existing endothelial
and the Center for RNA Therapeutics and Biology e
#Chemotherapy timing is key to success MIT researchers have devised a novel cancer treatment that destroys tumor cells by first disarming their defenses,
a professor of systems biology at the Technical University of Denmark who was not part of the research team. he latter is vital,
an MIT associate professor of biological engineering. here a general recognition that in order to understand the brain processes in comprehensive detail,
The company which aims to leverage biotechnology as a way to solve environmental issues is also modifying their system to generate value from wastewater in agricultural and military fields,
We are leveraging biotechnology to provide the highest return on investment for managing water. To that end, Cambrian is working on other projects that leverage exoelectrogenic microbes to treat wastewater.
Meeting at MIT in 2006 over a shared fondness for biotech, Silver, then a research scientist in MIT Space Systems Lab,
and Buck, a biological engineering graduate student, won a grant from the NASA Institute for Advanced Concepts program to create a life-support system that could treat waste
is to leverage biotechnology to advance a sustainable ndustrial ecology, where the waste of industry is recycled to create energy
and a member of MIT departments of biological engineering and of biology, Center for Environmental Health Sciences,
The researchers also anticipate that it could help scientists learn more about tumor biology. As opposed to just studying the genetic profile of tumor cells this could also reveal how they re interacting with the stroma that surrounds the tumor.
The researchers are now working on sensors that could be used to monitor other biological properties such as ph. We hope this is the first of many types of solid-state contrast agents where the material responds to its chemical environment in such a way that we can detect it by MRI Cima says.
(and wearing) bionic leg prostheses that he says emulate nature mimicking the functions and power of biological knees ankles and calves.
Initially developed by Herr s research group Biom s prosthesis dubbed the Biom T2 System simulates a biological ankle
#Erasing a genetic mutation Using a new gene-editing system based on bacterial proteins MIT researchers have cured mice of a rare liver disorder caused by a single genetic mutation.
The findings described in the March 30 issue of Nature Biotechnology offer the first evidence that this gene-editing technique known as CRISPR can reverse disease symptoms in living animals.
Researchers have copied this cellular system to create gene-editing complexes that include a DNA-cutting enzyme called Cas9 bound to a short RNA guide strand that is programmed to bind to a specific genome sequence telling Cas9 where to make its cut.
When the cell repairs the damage produced by Cas9 it copies from the template introducing new genetic material into the genome.
Scientists envision that this kind of genome editing could one day help treat diseases such as hemophilia Huntington s disease
and others that are caused by single mutations. Scientists have developed other gene-editing systems based on DNA-slicing enzymes also known as nucleases
Disease correctionfor this study the researchers designed three GUIDE RNA strands that target different DNA sequences near the mutation that causes type I tyrosinemia in a gene that codes for an enzyme called FAH.
and one of the lead authors of the Nature Biotechnology paper. This work shows that CRISPR can be used successfully in adults
and also identifies several of the challenges that will need to be addressed moving forward to the development of human therapies says Charles Gersbach an assistant professor of biomedical engineering at Duke university who was not part of the research team.
says Constance Cepko, a professor of genetics at Harvard Medical school. Previous efforts have focused on analyzing only a small number of cell types at a time,
which respond to their environment produce complex biological molecules and span multiple length scales with the benefits of nonliving materials
or diagnostic sensors says Timothy Lu an assistant professor of electrical engineering and biological engineering. Lu is the senior author of a paper describing the living functional materials in the March 23 issue of Nature Materials.
I think this is really fantastic work that represents a great integration of synthetic biology and materials engineering says Lingchong You an associate professor of biomedical engineering at Duke university who was not part of the research team.
The research was funded by the Office of Naval Research the Army Research Office the National Science Foundation the Hertz Foundation the Department of defense the National institutes of health and the Presidential Early Career Award for Scientists and Engineers s
According to Tim Lu, an assistant professor of electrical engineering and biological engineering at MIT, it boils down to the inefficient bacteria-detection assays used in the food industry.
Based on Lu graduate school research at MIT, the assay uses biological particles called bacteriophages, or phages,
or polymerase chain reactions (PCR, which copies DNA) may be efficient in one area, but lacking in the other two.
and for other means across other industries. hages are the most abundant biological particle On earth.
With the assay, Lu says Sample6 hopes to bring synthetic biology, and specifically phages, to microbial detection across many fields.
We want ultimately to democratize the use of synthetic biology in the real world he says i
Theye also used as biological probes to image cancer and to study processes inside cells,
Pentelute envisions that the technology could have an impact on synthetic biology comparable to rapid synthesis of short strands of DNA and RNA.
Strano and the paper lead author, postdoc and plant biologist Juan Pablo Giraldo, envision turning plants into self-powered, photonic devices such as detectors for explosives or chemical weapons.
Giraldo says. his is a marvelous demonstration of how nanotechnology can be coupled with synthetic biology to modify
a professor of biomedical engineering at Boston University who was involved not in the research. he authors nicely show that self-assembling nanoparticles can be used to enhance the photosynthetic capacity of plants,
Giraldo says. t an opportunity for people from plant biology and the chemical engineering nanotechnology community to work together in an area that has a large potential.
That decoupling of the two parameters he says is something that biologists had observed in real fish.
Video Melanie Gonick All of our algorithms and control theory are designed pretty much with the idea that we ve got rigid systems with defined joints says Barry Trimmer a biology professor at Tufts University who specializes in biomimetic soft robots.
MIT cancer biologists have discovered now that certain proteins in this structure, known as the extracellular matrix, help cancer cells make their escape.
Other authors are Steven Carr, director of the Proteomics Platform at the Broad Institute; Karl Clauser, a research scientist at the Broad Institute;
It dependent on modern technology having the genome sequences, having mass spectrometry machines that are really good,
This study utilizes the power of proteomics to identify extracellular matrix proteins critical in metastasis. Many of the proteins identified interact with cancer cells by binding to proteins called integrins that are found on cell surfaces,
This is a clever and inspired technology to develop new exogenous compounds that can detect clinical conditions with aberrantly high protease concentrations says Samuel Sia an associate professor of biological engineering at Columbia University who was involved not in the research.
Microbiologists have taken rarely into account fluid flow as an ecological parameter whereas physicists have started just recently to pay attention to microbes he says adding:
the better, says Darrell Irvine, a professor of biological engineering and of materials science and engineering, and the senior author of the paper.
or it could be that you re interrogating a biological sample and too much light could damage it.
but other biological systems are the same. There could also be remote-sensing applications where you may want to look at something
#Biologists ID new cancer weakness About half of all cancer patients have a mutation in a gene called p53
A new study from MIT biologists has found that tumor cells with mutated p53 can be made much more vulnerable to chemotherapy by blocking another gene called MK2.
and potentially useful approach for others to use says Titia de Lange a professor of cell biology
and genetics at Rockefeller University who was not part of the research team. Using these mice the researchers found that before treatment tumors lacking both MK2
and the Institute for Collaborative Biotechnologies through the U s army Research Office u
#Resistance is futile Cisplatin is given a chemotherapy drug to more than half of all cancer patients. The drug kills cells very effectively by damaging nuclear DNA but if tumors become resistant to cisplatin they often grow back.
and an author of a paper describing the findings in the Oct 31 online edition of the journal Biology & Chemistry.
Kelley a professor of biochemistry and pharmaceutical sciences at the University of Toronto. Lead authors are Simon Wisnovsky who received his Phd from the University of Toronto and MIT alumnus Justin Wilson Phd 13.
or replicate its genome. If enough of these blockages form the cell undergoes a type of programmed cell suicide called apoptosis
because they can interact with so many different biomolecules Radford says. By targeting specific cellular organelles with the same therapeutic molecules we can learn a lot about how the cells respond to a given compound
Eric Perreault, a professor of biomedical engineering and physical medicine and rehabilitation at Northwestern University, says the group findings present the first insight into how muscle activation alters the ankle mechanical properties over its normal range of motion,
Mutations in the gene for calcineurin have previously been found in some schizophrenia patients. Ten years ago MIT researchers led by Susumu Tonegawa the Picower Professor of Biology
and Neuroscience created mice lacking the gene for calcineurin in the forebrain; these mice displayed several behavioral symptoms of schizophrenia including impaired short-term memory attention deficits and abnormal social behavior.
and colleagues at the RIKEN-MIT Center for Neural Circuit Genetics at MIT s Picower Institute for Learning and Memory recorded the electrical activity of individual neurons in the hippocampus of these knockout mice
In the previous version of the system reported last December in Nature Biotechnology the researchers used mass spectrometry to distinguish the fragments by their mass.
The technology could also be useful for predicting recurrence of clots says Henri Spronk an assistant professor of biochemistry at Maastricht University in The netherlands.
Now, Semprus Biosciences, a startup co-founded by two MIT alumni Christopher Loose Phd 7
the biomaterial has positioned Semprus as a fast-growing biotech firm in Kendall Square. In its six years, the startup seed-funded, in part,
Seeing commercial potential, Langer a chemical engineer, bioengineer, and famed MIT entrepreneur layed matchmakerbetween Loose and Lucchino,
The research was funded by the National Institute of Biomedical Imaging and Bioengineering and Nanoscope Technologies, LLC n
The new technology is described in a paper appearing in the journal Nature Biotechnology, written by MIT Polina Anikeeva and 10 others.
For example, light could be transmitted through the optical channels to enable optogenetic neural stimulation, the effects
or silence neurons with pulses of light, a method called optogenetics. Activating the projections led to compulsive sucrose-eating
However, in recent years neuroscientists have shown in animal models that it is possible to reverse the debilitating effects of these gene mutations.
whether different gene mutations disrupt common physiological processes. If this were the case, a treatment developed for one genetic cause of autism
Different genes, same consequences Another cause of autism and intellectual disability is the loss of a series of genes on human chromosome 16,
Current research indicates that well over 100 distinct gene mutations can manifest as intellectual disability and autism.
where biomaterials are chosen and rationally designed to match specific tissue types and disease states. After characterizing the adhesive material performance in different diseased tissues,
Joseph Bonventre, chief of the renal unit and director of the bioengineering division at Brigham and Women Hospital in Boston, agrees that the study represents an important step toward a more personalized approach. ou want the best adhesive possible,
rather than developing biomaterials that try to work for all conditions. Doctors have begun using this kind of personalized approach
but it has not yet spread to the selection of biomaterials such as tissue glue. The MIT team now hopes to move the sealant into clinical trials
Fang says, of biomolecules placed on the hybrid material surface. Sheng Shen, an assistant professor of mechanical engineering at Carnegie mellon University who was involved not in this research,
and other biological components. n the biological domain, there are various molecules and atoms in contact with one another, sliding along like biomolecular motors,
as a result of friction or lack of friction, Gangloff says. o this intuition for how to arrange atoms so as to minimize
from the nanoscale to the macroscale. he applications and related impact of their novel method propels a huge variety of research fields investigating effects relevant from raft tectonics down to biological systems
Earlier this month, MIT spinout Microchips Biotech partnered with a pharmaceutical giant to commercialize its wirelessly controlled, implantable,
Invented by Microchips Biotech cofounders Michael Cima, the David H. Koch Professor of Engineering, and Robert Langer, the David H. Koch Institute Professor, the microchips consist of hundreds of pinhead-sized reservoirs,
and osteoporosis. Now Microchips Biotech will begin co-developing microchips with Teva Pharmaceutical, the world largest producer of generic drugs,
Microchips Biotech says these microchips could also improve medication-prescription adherence a surprisingly costly issue in the United states. A 2012 report published in the Annals of Internal medicine estimated that Americans who don stick to prescriptions rack up $100 billion to $289 billion
Microchips Biotech will continue work on its flagship product, a birth-control microchip, backed by the Bill and Melinda Gates Foundation,
Cima, who now serves on the Microchips Biotech board of directors with Langer, sees this hormone-releasing microchip as one of the first implantable rtificial organsecause it acts as a gland. lot of the therapies are trying to chemically trick the endocrine systems Cima says. e are doing that with this artificial organ we created. ild ideasinspiration for the microchips came in the late 1990s,
For years, the technology underwent rigorous research and development at Microchips Biotech. But in 2011, Langer and Cima,
EMS innovationsmicrochips Biotech made several innovations in the microelectromechanical systems (MEMS) manufacturing process to ensure the microchips could be commercialized.
To do so, Microchips Biotech modified a cold-welding ongue and grooveprocess. This meant depositing a soft,
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