and bind with particular molecules within the body such as markers for tumor cells or other disease agents.
For example the coating could have a molecule that binds to a specific type of tumor cells;
so you could see the spatial macroscopic outlines of a tumor he says. The next step for the team is to test the new nanoparticles in a variety of biological settings.
then the cable can get taut and fracture, which is really bad news . So we wanted to understand what was underlying those patterns.
which, when wound on a spool, retains a certain amount of curve as it unwound.
This type of high-speed screen could help overcome one of the major bottlenecks in developing disease treatments based on biologics:
#Fish on the flyzebrafish are used commonly to model human diseases in part because their larvae are transparent making it easy to see the effects of genetic mutations or drugs.#
For this study Yanik s team developed a new technology to inject RNA carried by nanoparticles called lipidoids previously designed by Daniel Anderson an associate professor of chemical engineering member of the Koch Institute for Integrative Cancer Research and Institute
These fatty molecules have shown promise as delivery vehicles for RNA interference a process that allows disease-causing genes to be turned off with small strands of RNA.#
This approach should have utility across multiple disease areas. New leadsthe researchers are now using
#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
Cancer Institute and the Broad Institute. This finding which suggests that muscle tissue is broken down in the disease s earliest stages could offer new insights into developing early diagnostics for pancreatic cancer which kills about 40000 Americans every year
and is caught usually not until it is too late to treat. The study which appears today in the journal Nature Medicine is based on an analysis of blood samples from 1500 people participating in long-term health studies.
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
We found that higher levels of branched chain amino acids were present in people who went on to develop pancreatic cancer compared to those who did not develop the disease Wolpin says.
These findings led us to hypothesize that the increase in branched chain amino acids is due to the presence of an early pancreatic tumor.
Using those mouse models we found that we could perfectly recapitulate these exact metabolic changes during the earliest stages of cancer Vander Heiden says.
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.
which has not been seen in other types of cancer occurs in the early stages of pancreatic cancer.
They suspect that pancreatic tumors may be trying to feed their own appetite for amino acids that they need to build cancerous cells.
The findings may also allow scientists to pursue new treatments that would work by targeting tumor metabolism
and cutting off a tumor s nutrient supply Vander Heiden says. MIT s contribution to this research was funded by the Lustgarten Foundation the National institutes of health the Burroughs Wellcome Fund and the Damon Runyon Cancer Research Foundation n
#Underwater robot for port security Last week at the International Conference on Intelligent Robots and Systems MIT researchers unveiled an oval-shaped submersible robot a little smaller than a football with a flattened
Each year these superbugs including drug-resistant forms of tuberculosis and staphylococcus infect more than 2 million people nationwide
Using a gene-editing system that can disable any target gene they have shown that they can selectively kill bacteria carrying harmful genes that confer antibiotic resistance or cause disease.
and they envision that eventually the technology could be adapted to deliver the CRISPR components to treat infections or remove other unwanted bacteria in human patients.
We re excited about the application of Combigem to probe complex multifactorial phenotypes such as stem cell differentiation cancer biology
To train the material Holschuh first wound raw SMA fiber into extremely tight millimeter-diameter coils then heated the coils to 450 degrees Celsius to set them into an original or trained shape.
If your suit happens to have sensors it could tourniquet you in the event of injury without you even having to think about it.
#A new way to diagnose malaria Over the past several decades malaria diagnosis has changed very little.
which causes the disease. This approach gives an accurate count of how many parasites are in the blood an important measure of disease severity
but is not ideal because there is potential for human error. A research team from the Singapore-MIT Alliance for Research
This technique could offer a more reliable way to detect malaria says Jongyoon Han a professor of electrical engineering and biological engineering at MIT.
Hunting malaria with magnetswith the traditional blood-smear technique a technician stains the blood with a reagent that dyes cell nuclei.
However the technology and expertise needed to identify the parasite are not always available in some of the regions most affected by malaria
Tracking infectionhemozoin crystals are produced in all four stages of malaria infection including the earliest stages
Also the amount of hemozoin can reveal how severe the infection is or whether it is responding to treatment.
This circuit could offer a target for new drugs to help treat conditions such as posttraumatic stress disorder the researchers say In the future one may be able to develop methods that help people to remember positive memories more strongly than negative ones says Susumu Tonegawa the Picower
and posttraumatic stress disorder but the neural circuitry underlying such malleability is known not. In this study the researchers set out to explore that malleability with an experimental technique they recently devised that allows them to tag neurons that encode a specific memory or engram.
whether reactivating pleasant memories has any effect on depression in hopes of identifying new targets for drugs to treat depression and posttraumatic stress disorder.
and also has potential implications for treating mental illness. This is a tour de force of modern molecular-biology-based methods for analyzing processes such as learning and memory at the neural-circuitry level.
Their device, about the size of a dime, could be used to detect the extremely rare tumor cells that circulate in cancer patientsblood,
whether a tumor is going to spread. Separating cells with sound offers a gentler alternative to existing cell-sorting technologies,
To test whether the device could be useful for detecting circulating tumor cells, the researchers tried to separate breast cancer cells known as MCF-7 cells from white blood cells.
the researchers plan to test it with blood samples from cancer patients to see how well it can detect circulating tumor cells in clinical settings.
A 1-milliliter sample of blood may contain only a few tumor cells. f you can detect these rare circulating tumor cells,
it a good way to study cancer biology and diagnose whether the primary cancer has moved to a new site to generate metastatic tumors,
Dao says. his method is a step forward for detection of circulating tumor cells in the body.
It has the potential to offer a safe and effective new tool for cancer researchers, clinicians and patients,
Suresh says. The research was funded by the National institutes of health and the National Science Foundation a
#Unlocking the potential of simulation software With a method known as finite element analysis (FEA), engineers can generate 3-D digital models of large structures to simulate how theyl fare under stress, vibrations, heat,
and other real-world conditions. Used for mapping out large-scale structures such as mining equipment, buildings, and oil rigs these simulations require intensive computation done by powerful computers over many hours, costing engineering firms much time and money.
In one demonstration, for instance, a mining company used components available in the Akselos library to rapidly create a simulation of shiploader infrastructure complete with high-stress ot spotsthat needed inspection.
so they can visualize the stress, strain, and displacement in 3-D in their browser, he says. e think it a great way to show students the value of fast, 3-D simulations.
However delivering these small RNAS to solid tumors remains a significant challenge as the RNAS must target the correct cells
This week in the journal Proceedings of the National Academy of Sciences researchers at the Koch Institute for Integrative Cancer Research at MIT report that they have delivered successfully small RNA therapies in a clinically relevant mouse model of lung cancer to slow
and shrink tumor growth. Their research offers promise for personalized RNA combination therapies to improve therapeutic response.
and tumor-suppressor gene p53 is deleted researchers injected mice with RNA-carrying nanoparticles. This mouse model reflects many of the hallmarks of human lung cancer
They found that delivery of mir-34a a p53-regulated mirna slowed tumor growth as did delivery of sikras a KRAS-targeting sirna.
Instead of just slowing tumor growth this combination therapy caused tumors to regress and shrink to about 50 percent of their original size.
Potential for personalized cancer treatmentsthis early example of RNA combination therapy demonstrates the potential of developing personalized cancer treatments.
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.
Small-RNA therapy holds great promise for cancer Jacks#says. It is appreciated widely that the major hurdle in this field is efficient delivery to solid tumors outside of the liver
and this work goes a long way in showing that this is achievable. RNA therapies are very flexible
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
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
and engineers Langer#says. It s an example of what makes the Koch Institute very special.
This research was supported by grant funding from the National institutes of health and the National Cancer Institute e
#New analysis reveals tumor weaknesses Scientists have known for decades that cancer can be caused by genetic mutations
but more recently they have discovered that chemical modifications of a gene can also contribute to cancer.
Analyzing these modifications can provide important clues to the type of tumor a patient has
For example patients with glioblastoma a type of brain tumor respond well to a certain class of drugs known as alkylating agents
In some cancers the MGMT gene is turned off when methyl groups attach to specific locations in the DNA sequence namely cytosine bases that are adjacent to guanine bases.
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.
#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.
Plasmodium falciparum a blood-borne parasite carried by mosquitoes is responsible for most of the estimated 219 million cases and 655000 deaths from malaria per year.
CRISPR a gene-editing system devised within the past several years exploits a set of bacterial proteins that protect microbes from viral infection.
and eba-175 that had previously been knocked out in malaria using traditional approaches. The kahrp gene produces a protein that causes red blood cells
when infected with malaria. Niles team was able to disrupt this gene in 100 percent of parasites treated with the CRISPR system;
#A new way to model cancer Sequencing the genomes of tumor cells has revealed thousands of mutations associated with cancer.
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.
In a study appearing in the Aug 6 issue of Nature the researchers generated liver tumors in adult mice by disrupting the tumor suppressor genes p53 and pten.
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.
The sequencing of human tumors has revealed hundreds of oncogenes and tumor suppressor genes in different combinations.
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.
Gene disruptioncrispr relies on cellular machinery that bacteria use to defend themselves from viral infection.
To investigate the potential usefulness of CRISPR for creating mouse models of cancer the researchers first used it to knock out p53 and pten
Previous studies have shown that genetically engineered mice with mutations in both of those genes will develop cancer within a few months.
and pten the researchers were able to disrupt those two genes in about 3 percent of liver cells enough to produce liver tumors within three months.
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.
This is a game-changer for the production of engineered strains of human cancer says Ronald Depinho director of the University of Texas MD Anderson Cancer Center who was not part of the research team.
Enhanced potential of this powerful technology will be realized with improved delivery methods the testing of#CRISPR/Cas9 efficiency in other organs and tissues and the use of CRISPR/Cas9 in tumor-prone backgrounds.
The research was funded by the National institutes of health and the National Cancer Institute u
#New material structures bend like microscopic hair MIT engineers have fabricated a new elastic material coated with microscopic hairlike structures that tilt in response to a magnetic field.
Still others could help children with autism better interact el Kaliouby says such as games that make people match facial cues with emotions.
Together they quickly started applying the facial-coding technology to autism research and training the algorithms by collecting vast stores of data.
#$650 million commitment to Stanley Center at Broad Institute aims to galvanize mental illness research The following is adapted from a press release issued today by the Broad Institute of MIT and Harvard.
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.
Years of frustration give way to progressmental illness exacts an enormous human toll. The leading cause of disability in the United states it affects millions
and most often strikes patients while they are young and otherwise healthy. Biomedical researchers have struggled for years to understand the molecular causes of serious ailments such as schizophrenia and bipolar disorder.
Until five years ago there was no clear scientific evidence around even a single gene that contributes to causing either disorder.
Yet in the past few years scientists have begun to find genes that shape the risk of schizophrenia bipolar disorder and other illnesses thanks in large part to Stanley s support.
and assembled the world s largest collection of DNA samples in psychiatric research currently more than 175000 samples including schizophrenia bipolar disorder autism attention deficit hyperactivity disorder and healthy control samples.
Analysis of 80000 of these samples so far by Broad researchers and collaborators has linked more than 100 genomic regions to schizophrenia
Significant efforts are ramping up in bipolar disorder autism and other conditions. 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
when his son Jonathan was stricken with severe bipolar disorder while in college. The first few years were difficult
but Jonathan overcame his illness with the help of lithium a landmark drug first used to treat patients with mental illness in 1949.
Now a successful attorney Jonathan is also a founding board member of the Treatment Advocacy Center a nonprofit organization dedicated to reforming laws that affect persons with a mental illness and an advocate for the National Alliance on Mental illness.
Although lithium helped give Jonathan a normal life other patients who suffer from mental illness have not been as fortunate.
When Edward Scolnick met the Stanleys he had had a stellar career first in cancer research in the 1970s and then as one of the most respected scientists in the pharmaceutical industry.
the first vaccine against cervical cancer; and many other breakthroughs. Instead of retiring Scolnick took on a new challenge:
He moved to the Broad Institute to tackle mental illness because he had a deep personal interest in the field.
Early in his career Scolnick had helped launch a revolution in cancer research based on the discovery of the first cancer genes.
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.
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.
Beth Israel Deaconess Medical center Boston Children s Hospital Brigham and Women s Hospital Dana-Farber Cancer Institute and Massachusetts General Hospital.
Broad investigators have led international consortia that have found thousands of genetic variants responsible for common diseases such as diabetes heart disease
and Crohn s disease and translated that knowledge into descriptions of the underlying biological processes a critical step in the development of rationally designed drugs.
They have discovered several hundred genes that are mutated in cancer and applied this knowledge to begin to invent new targeted forms of therapy.
Complete the list of all genes that play roles in severe psychiatric disorders including schizophrenia bipolar disorder autism and others.
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.
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
About the Stanley Center for Psychiatric Research The mission of the Stanley Center for Psychiatric Research at the Broad Institute is to reduce the burden of serious mental illness through research.
Stanley Center researchers focus on schizophrenia bipolar disorder autism attention deficit hyperactivity disorder and other neuropsychiatric disorders.
in order to understand disease mechanisms identify potential biomarkers and ignite needed progress in therapeutics. Launched in 2007 by a $100 million commitment from the Stanley Medical Research Institute the Stanley Center has extensive collaborations with investigators at MIT Harvard and the Harvard-affiliated hospitals as well as with investigators around the world.
discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics;
Currently a patient who has experienced a heart attack or weakening of the heart has wires running from the implant to a charger
which means risk for infection. In our case a patient could lie on the bed
This noninvasive approach could pave the way to using optogenetics in human patients to treat epilepsy and other neurological disorders,
In addition, it is difficult to perform long-term studies of chronic diseases with these implants. To find a better alternative, Boyden, graduate student Amy Chuong,
In people with a disease called retinitis pigmentosa, cones slowly atrophy, eventually causing blindness. Friedrich Miescher Institute scientists Botond Roska and Volker Busskamp have shown previously that some vision can be restored in mice by engineering those cone cells to express light-sensitive proteins.
making it potentially more useful for treating retinitis pigmentosa. This type of noninvasive approach to optogenetics could also represent a step toward developing optogenetic treatments for diseases such as epilepsy,
which could be controlled by shutting off misfiring neurons that cause seizures, Boyden says. ince these molecules come from species other than humans,
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
for any brain disorder, the exact set of cells involved, Boyden says. he ability to survey activity throughout a nervous system may help pinpoint the cells
or networks that are involved with a brain disorder, leading to new ideas for therapies. Boyden team developed the brain-mapping method with researchers in the lab of Alipasha Vaziri of the University of Vienna and the Research Institute of Molecular Pathology in Vienna.
The paper lead authors are Young-Gyu Yoon, a graduate student at MIT, and Robert Prevedel, a postdoc at the University of Vienna.
holds great potential for treating many diseases caused by malfunctioning genes. However, it has been difficult for scientists to find safe and effective ways to deliver gene-blocking RNA to the correct targets.
Up to this point, researchers have gotten the best results with RNAI targeted to diseases of the liver,
This raises the possibility of using RNAI to treat many types of disease, including cancer and cardiovascular disease,
the researchers say. here been a growing amount of excitement about delivery to the liver in particular,
says Daniel Anderson, the Samuel A. Goldblith Associate professor of Chemical engineering, a member of MIT Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science,
400 variants of their particles in cervical cancer cells by measuring whether they could turn off a gene coding for a fluorescent protein that had been added to the cells.
To demonstrate the potential for treating lung disease, the researchers used the nanoparticles to block two genes that have been implicated in lung cancer VEGF receptor 1 and Dll4,
which promote the growth of blood vessels that feed tumors. By blocking these in lung endothelial cells,
the researchers were able to slow lung tumor growth in mice and also reduce the spread of metastatic tumors.
and learn more about diseases of endothelial tissue such as atherosclerosis and diabetic retinopathy, which can cause blindness. ndothelial cells play a very important role in multiple steps of many diseases, from initiation to the onset of clinical complications,
says Aikawa, who was not part of the research team. his kind of technology gives us an extremely powerful tool that can help us understand these devastating vascular diseases.
The researchers plan to test additional potential targets in hopes that these particles could eventually be deployed to treat cancer, atherosclerosis,
and other diseases. Scientists from Alnylam Pharmaceuticals and Harvard Medical school also contributed to the study,
which was funded by a National Defense Science and Engineering Fellowship, the National Science Foundation, MIT Presidential Fellowships, the National institutes of health, the Stop and Shop Pediatric Brain tumor Fund,
the Pediatric Brain Tumour Fund, the Deutsche Forschungsgemeinschaft, Alnylam, 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,
dramatically shrinks lung and breast tumors. The MIT team, led by Michael Yaffe, the David H. Koch Professor in Science,
who is a member of MIT Koch Institute for Integrative Cancer Research. ee moving from the simplest model of the nanoparticle just getting the drug in there
and targeting it to having smart nanoparticles that deliver drug combinations in the way that you need to really attack the tumor.
Doctors routinely give cancer patients two or more different chemotherapy drugs in hopes that a multipronged attack will be more successful than a single drug.
which shuts down one of the pathways that promote uncontrolled tumor growth. These pretreated tumor cells were much more susceptible to treatment with a DNA-damaging drug called doxorubicin than cells given the two drugs simultaneously. t like rewiring a circuit,
says Yaffe, who is also a member of the Koch Institute. hen you give the first drug,
found on tumor cell surfaces, has been approved by the Food and Drug Administration to treat pancreatic cancer and some types of lung cancer.
Doxorubicin is used to treat many cancers, including leukemia, lymphoma, and bladder, breast, lung, and ovarian tumors.
Staggering these drugs proved particularly powerful against a type of breast cancer cell known as triple-negative,
which doesn have overactive estrogen, progesterone, or HER2 receptors. Triple-negative tumors, which account for about 16 percent of breast cancer cases,
are much more aggressive than other types and tend to strike younger women. That was an exciting finding
ow do you translate that into something you can actually give a cancer patient? From lab result to drug delivery To approach this problem,
folate, helps direct the particles to tumor cells, which express high quantities of folate receptors.
Once the particles reach a tumor and are taken up by cells, the particles start to break down.
The researchers tested the particles in mice implanted with two types of human tumors: triple-negative breast tumors and non-small-cell lung tumors.
Both types shrank significantly. Furthermore, packaging the two drugs in liposome nanoparticles made them much more effective than the traditional forms of the drugs,
even when those drugs were given in a time-staggered order. his particle delivery system not only provides a platform for time-staggered treatment strategies in cancer,
but also for delivering the drugs more directly to the tumor tissue itself, says Rune Linding,
As a next step before possible clinical trials in human patients, the researchers are now testing the particles in mice that are programmed genetically to develop tumors on their own,
instead of having human tumor cells implanted in them. The researchers believe that time-staggered delivery could also improve other types of chemotherapy.
and ovarian cancers. At the same time, Hammond lab is working on more complex nanoparticles that would allow for more precise loading of the drugs
The work was funded by the National institutes of health, the Center for Cancer Nanotechnology Excellence, the Koch Institute Frontier Research Program supported by the Kathy and Curt Marble Fund for Cancer Research,
and a Breast cancer Alliance Exceptional Project Grant
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