Synopsis: Biotech:


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ut it was really interesting to learn about how they were trying to solve this problem from a biological standpoint,


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They also found higher rates of apoptosis or programmed cell death in tumor cells near the capsules.


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if we could create a synthetic active system that could sense gradients in biological receptors Alexander-Katz explains.


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#Fast modeling of cancer mutations Sequencing the genomes of tumor cells has revealed thousands of genetic mutations linked with cancer.

However sifting through this deluge of information to figure out which of these mutations actually drive cancer growth has proven to be a tedious time-consuming process.

MIT researchers have developed now a new way to model the effects of these genetic mutations in mice.

Their approach based on the genome-editing technique known as CRISPR is much faster than existing strategies

which require genetically engineering mice that carry the cancerous mutations. It s a very rapid and very adaptable approach to make models says Thales Papagiannakopoulos a postdoc at MIT s Koch Institute for Integrative Cancer Research

With a lot of these mutations we have no idea what their role is in tumor progression.

If we can actually understand the biology we can then go in and try targeted therapeutic approaches.

Cutting out cancer genescrispr originally discovered by biologists studying the bacterial immune system involves a set of proteins that bacteria use to defend themselves against bacteriophages (viruses that infect bacteria.

Scientists have begun recently exploiting this system to make targeted mutations in the genomes of living animals either deleting genes

This process is much faster than generating mice with mutations inserted at the embryonic stem cell stage

This is#a wonderful new example of the power of the CRISPR approach says Anton Berns a professor of molecular genetics at The netherlands Cancer Institute.

The cancer genome sequence initiative provides us with numerous candidate genes that might modulate tumorigenesis and we need a rapid method to test their contribution.

This method also offers new ways to seek personalized treatments for cancer patients depending on the types of mutations found in their tumors the researchers say.

This opens up a whole new field of being personalized able to do oncology where you can model human mutations

and start treating tumors based on these mutations Papagiannakopoulos says. The research was funded by the Howard Hughes Medical Institute the Ludwig Center for Molecular Oncology at MIT and the National Cancer Institute u


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including bladder cancer. rology hasn gotten really the benefit of improvement in the biotech revolution. This type of technology can revolutionize how we do drug therapy in urology,

Indeed, collecting clinical data is a major challenge in spinning biotechnology out of the lab, notes Cima,


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#Nanoparticles get a magnetic handle A long-sought goal of creating particles that can emit a colorful fluorescent glow in a biological environment

Compactness is critical for biological and a lot of other applications. In addition previous efforts were unable to produce particles of uniform and predictable size

The new method produces the combination of desired properties in as small a package as possible Bawendi says which could help pave the way for particles with other useful properties such as the ability to bind with a specific type of bioreceptor or another

Initially at least the particles might be used to probe basic biological functions within cells Bawendi suggests.

Melanie Gonick/MIT The ability to manipulate the particles with electromagnets is key to using them in biological research Bawendi explains:

The next step for the team is to test the new nanoparticles in a variety of biological settings.


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This work goes a long way to squeezing the last drop of ethanol from sugar adds Gerald Fink an MIT professor of biology member of the Whitehead Institute and the paper s other senior author.

They also found that these changes did not affect the biochemical pathway used by the yeast to produce ethanol:


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#High-speed biologics screen MIT engineers have devised a way to rapidly test hundreds of different drug-delivery vehicles in living animals making it easier to discover promising new ways to deliver a class of drugs called biologics

In a study appearing in the journal Integrative biology the researchers used this technology to identify materials that can efficiently deliver RNA to zebrafish and also to rodents.

This type of high-speed screen could help overcome one of the major bottlenecks in developing disease treatments based on biologics:

Biologics is the fastest growing field in biotech because it gives you the ability to do highly predictive designs with unique targeting capabilities says senior author Mehmet Fatih Yanik an associate professor of electrical engineering and computer science and biological engineering.

However delivery of biologics to diseased tissues is challenging because they are significantly larger and more complex than conventional drugs.

By combining this work with our previously published high-throughput screening system we are able to create a drug-discovery pipeline with efficiency we had imagined never before adds Tsung-Yao Chang a recent MIT Phd recipient and one of the paper s lead authors.

because their larvae are transparent making it easy to see the effects of genetic mutations or drugs.#

and other small animals have teamed up with Anderson et al. who are leading experts in RNA delivery to create a new platform for rapidly screening biologics

Yanik s lab is currently using this technology to find delivery vehicles that can carry biologics across the blood-brain barrier a very selective barrier that makes it difficult for drugs


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#Biologists find an early sign of cancer Years before they show any other signs of disease pancreatic cancer patients have very high levels of certain amino acids in their bloodstream according to a new study from MIT Dana-Farber

What that means for the tumor and what that means for the health of the patient those are long-term questions still to be answered says Matthew Vander Heiden an associate professor of biology a member of MIT s Koch Institute for Integrative Cancer Research

This is a finding of fundamental importance in the biology of pancreatic cancer says David Tuveson a professor at the Cancer Center at Cold Spring Harbor Laboratory who was involved not in the work.


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if this type of technology could find use in domestic maritime operations ranging from the detection of smuggled nuclear biological


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Led by Timothy Lu an associate professor of biological engineering and electrical engineering and computer science the researchers described their findings in the Sept. 21 issue of Nature Biotechnology.

Last month Lu s lab reported a different approach to combating resistant bacteria by identifying combinations of genes that work together to make bacteria more susceptible to antibiotics.

In the new Nature Biotechnology study graduate students Robert Citorik and Mark Mimee worked with Lu to target specific genes that allow bacteria to survive antibiotic treatment.

The CRISPR genome-editing system presented the perfect strategy to go after those genes. CRISPR originally discovered by biologists studying the bacterial immune system involves a set of proteins that bacteria use to defend themselves against bacteriophages (viruses that infect bacteria.

One of these proteins a DNA-cutting enzyme called Cas9 binds to short RNA guide strands that target specific sequences telling Cas9 where to make its cuts.

The genes encoding NDM-1 and other antibiotic resistance factors are carried usually on plasmids circular strands of DNA separate from the bacterial genome making it easier for them to spread through populations.

They also successfully targeted another antibiotic resistance gene encoding SHV-18 a mutation in the bacterial chromosome providing resistance to quinolone antibiotics and a virulence factor in enterohemorrhagic E coli.

which in principle could help to combat the spread of antibiotic resistance fueled by excessive broad-spectrum treatment says Ahmad Khalil an assistant professor of biomedical engineering at Boston University who was not part of the research team.

We re excited about the application of Combigem to probe complex multifactorial phenotypes such as stem cell differentiation cancer biology


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bumpy texture, can quickly remove more than 90 percent of the biological fouling. Zhenan Bao, a professor of chemical engineering at Stanford university who was involved not in this research,


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This technique could offer a more reliable way to detect malaria says Jongyoon Han a professor of electrical engineering and biological engineering at MIT.

It s based on a naturally occurring biomarker that does not require any biochemical processing of samples says Han one of the senior authors of a paper describing the technique in the Aug 31 issue of Nature Medicine.


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Furthermore the researchers found that they could reverse the emotional association of specific memories by manipulating brain cells with optogenetics a technique that uses light to control neuron activity.

Professor of Biology and Neuroscience director of the RIKEN-MIT Center for Neural Circuit Genetics at MIT s Picower Institute for Learning and Memory and senior author of the paper.#

#The paper s lead authors are Roger Redondo a Howard Hughes Medical Institute postdoc at MIT and Joshua Kim a graduate student in MIT s Department of biology.

David Anderson a professor of biology at the California Institute of technology says the study makes an important contribution to neuroscientists fundamental understanding of the brain


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it a good way to study cancer biology and diagnose whether the primary cancer has moved to a new site to generate metastatic tumors,


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It was developed originally in the laboratory of Koch Institute Director#Tyler Jacks the#David H. Koch Professor of Biology#who is co-senior author of this paper.

With efficient delivery of therapeutic RNA any individual small RNA or combination of RNAS could be deployed to regulate the genetic mutations underlying a given patient s cancer.

because you can design them to treat any type of disease by modifying gene expression very specifically says James Dahlman a graduate student in Anderson s

This investigation typifies the Koch Institute s model of bringing biologists and engineers together to engage in interdisciplinary cancer research.

This study is a terrific example of the potential of new RNA therapies to treat disease that was done in a highly collaborative way between biologists


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#New analysis reveals tumor weaknesses Scientists have known for decades that cancer can be caused by genetic mutations

These alterations known as epigenetic modifications control whether a gene is turned on or off. Analyzing these modifications can provide important clues to the type of tumor a patient has

if the DNA-repair gene MGMT is silenced by epigenetic modification. A team of MIT chemical engineers has developed now a fast reliable method to detect this type of modification known as methylation which could offer a new way to choose the best treatment for individual patients.

Beyond the genomeafter sequencing the human genome scientists turned to the epigenome the chemical modifications including methylation that alter a gene s function without changing its DNA sequence.

The other key component of Sikes system is a biochip a glass slide coated with hundreds of DNA PROBES that are complementary to sequences from the gene being studied.

When a DNA sample is exposed to this chip any strands that match the target sequences are trapped on the biochip.

This technique which cuts the amount of time required to analyze epigenetic modifications could be a valuable research tool as well as a diagnostic device for cancer patients says Andrea Armani a professor of chemical engineering

of which epigenetic markers are linked to which diseases. The MIT team is now adapting the device to detect methylation of other cancer-linked genes by changing the DNA sequences of the biochip probes.

They also hope to create better versions of the MBD protein and to engineer the device to require less DNA.


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#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


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#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.


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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.


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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.


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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

and bipolar disorder represent the best way to gain molecular insights into these disorders. 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.

Since 2004 Ted Stanley and his late wife Vada Stanley have been instrumental to the progress made thus far in identifying the genetic risk factors for schizophrenia and bipolar disorder and the initiation of therapeutic efforts based on those discoveries.

Stanley s new commitment is the culmination of a 25-year personal mission to discover the biology of psychiatric disorders

Human genomics has begun to reveal the causes of these disorders. We still have a long way to go

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


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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.


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#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,


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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.


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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


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#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,


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an MIT associate professor of biological engineering. here a general recognition that in order to understand the brain processes in comprehensive detail,


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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


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and a member of MIT departments of biological engineering and of biology, Center for Environmental Health Sciences,

here an opportunity to use these multiplexed plasmids in biological assays where several repair pathways can be probed at the same time,


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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.


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(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


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