#Protein Structures Assemble and Disassemble On Command Scientists have deciphered the genetic code that instructs proteins to either self-assemble
or disassemble in response to environmental stimuli, such as changes in temperature, salinity or acidity. The discovery provides a new platform for drug delivery systems and an entirely different view of cellular functions.
The advance was made by researchers at Duke university and is the first time that scientists have reported the ability to create biological structures that are programmed readily to assemble
and disassemble. With this knowledge in hand, researchers have opened a new world for designer proteins and investigations into nanotechnology
biotechnology and medical treatments. The study appears September 21 in Nature Materials. he very simple design rules that we have discovered provide a powerful engineering tool for many biomedical
and biotechnology applications, said Ashutosh Chilkoti, chair of the Department of Biomedical engineering at Duke. e can now,
with a flick of a switch and a temperature jump, make a huge range of biological molecules that either assemble
or disassemble. The study investigated several triggers that can cause protein structures to assemble or break apart,
but it primarily focused on heat. Protein-based structures that self-assemble when heated and remain stable inside of the bloodstream have long been used in a variety of applications.
The opposite behavior however, has eluded long researchers, especially outside of the carefully controlled environment of a chemistry lab. obody has been able to make these kinds of materials with the degree of complexity that we have demonstrated now,
said Felipe Garcia Quiroz, a former graduate student in Chilkoti laboratory and first author of the new study.
Chilkoti lab has designed self-assembling proteins for drug delivery systems for several years. Simply by adding heat,
these new packing materials put themselves together and help control where and when drugs are released inside the body through non-temperature-related mechanisms such as changes in acidity levels.
With the new discovery however, drugs could be encapsulated in protein cages that accumulate inside of a tumor and dissolve once heated.
Not only would this provide a more accurate way of delivering drugs, but the cages themselves could be used therapeutically. hese packaging systems have always been inert,
but now we can make these materials from bioactive components, said Quiroz. nce the cages get there
they could break down into additional therapeutic agents. We can now design two things into one.
Because the laboratory identified the genetic sequences that encode this behavior they were able to point out a long list of human proteins that likely exhibit it. his paper shows the incredible richness of peptide sequences that already have this very simple switch,
however, remains an open question. hese findings will be exciting to both the materials science and the biochemistry communities, said Quiroz. heyl be able to push the limits of what we know about these kinds of materials
and then go back to explore how biology is already making use of them. This work was funded by the National institutes of health and the National Science Foundation
through the Research Triangle MRSEC t
#Targeting DNA MIT biological engineers have developed a modular system of proteins that can detect a particular DNA sequence in a cell
and then trigger a specific response, such as cell death. This system can be customized to detect any DNA sequence in a mammalian cell
and then trigger a desired response, including killing cancer cells or cells infected with a virus,
James Collins, the Termeer Professor of Medical Engineering and Science in MIT Department of Biological engineering and Institute of Medical Engineering and Science (IMES).
To achieve this, the researchers could program the system to produce proteins that alert immune cells to fight the infection,
a professor of biotechnology and bioengineering at The swiss Federal Institute of technology in Zurich, described this experiment as an legant proof of conceptthat could lead to greatly improved treatments for viral infection. entinel designer cells engineered with the DNA sense
This would represent a quantum leap in antiviral therapy, said Fussenegger, who was involved not in the study.
While treating diseases using this system is likely many years away, it could be used much sooner as a research tool,
whether genetic material has been delivered successfully to cells that scientists are trying to genetically alter. Cells that did not receive the new gene could be induced to undergo cell death,
or to study the 3-D structure of normal chromosomes by testing whether two genes located far from each other on a chromosome fold in such a way that they end up next to each other,
the researchers say
#Researchers Discover Method to Measure Stiffness of Arteries in the Brain UCLA researchers have discovered a noninvasive method to measure vascular compliance,
a finding that may have ramifications for preventing stroke and the early diagnoses of Alzheimer disease.
or comply with the blood pressure changes as elastic arteries are said study senior author Danny J. J. Wang,
an associate professor of neurology and a researcher in the Ahmanson-Lovelace Brain Mapping Center at UCLA. ascular compliance is a useful marker for a number of cardiovascular diseases,
such as hypertension and diabetes, Wang said. rowing evidence suggests intracranial vascular pathology also may be associated with the origin and progression of cerebrovascular disorders and neurodegenerative diseases, such as Alzheimer disease,
The study appears this week in the peer-reviewed journal Neuroimage. The UCLA team compared stiffness measurements in young and elderly patients,
This finding is consistent with the theory that aging is associated with stiffening of the arteries.
the aorta. e hope our technique can provide an early marker for a number of socioeconomically important diseases like Alzheimer,
an assistant researcher in the UCLA Department of Neurology. number of studies suggest that vascular dysfunctions,
The development of early bio-or imaging markers for Alzheimer is of great importance for slowing disease progression.
Hardened arteries due to the accumulation of plaques on the vessel walls also is linked to cerebrovascular disorders such as stroke.
The need for a new approach to treatment of Alzheimer disease is urgent. Alzheimer is the most common age-related dementia
and the number of cases in the United states is expected to increase from the current number of about five to six million to 15 million by 2050.
The costs to family life and on the health care system are enormous. Alzheimer and other dementias are projected to cost the United states $226 billion in 2015 alone,
with that number rising to as high as $1. 1 trillion in 2050. The study was funded by the National institutes of health and the California Department of public health m
. professor of developmental and stem cell biology and director of the Eli and Edyth Broad Center of Regeneration Medicine and Stem Cell Research at UCSF. ooking at these early stages in development is the best opportunity to understand our brain evolution.
Building a brain from the inside out The grand architecture of the human cortex with its hundreds of distinct cell types, begins as a uniform layer of neural stem cells and builds itself from the inside out during several months of embryonic development.
They identified gene expression profiles typical of different types of neurons newborn neural progenitors and radial glia,
The gene activity profiles also provided several novel insights into the biology of outer radial glia.
For example, researchers had previously been puzzled as to how org cells could maintain their generative vitality so far away from the nurturing VZ. n the mouse,
But the new data reveals that orgs bring a support group with them: The cells express genes for surface markers and molecular signals that enhance their own ability to proliferate,
the researchers found. his is a surprising new feature of their biology, Pollen said. hey generate their own stem cell niche.
and showed that these cells are prolific neuron factories. In contrast to mouse vrgs, which produce 10 to 100 daughter cells during brain development,
a single human org can produce thousands of daughter neurons, as well as glial cellson-neuronal brain cells increasingly recognized as being responsible for a broad array of maintenance functions in the brain.
development and disease The discovery of human orgsself-renewing niche and remarkable generative capacity reinforces the idea that these cells may have been responsible for the expansion of the cerebral cortex in our primate ancestors,
Such techniques have the potential to enhance research into the origins of neurodevelopmental and neuropsychiatric disorders such as microcephaly, lissencephaly, autism and schizophrenia,
which are thought to affect cell types not found in the mouse models that are used often to study such diseases.
a common brain cancer whose ability to grow, migrate and hack into the brain blood supply appears to rely on a pattern of gene activity similar to that now identified in these neural stem cells. he cerebral cortex is so different in humans than in mice,
or in diseases of the cerebral cortex, this is a really exciting discovery. The study represents the first salvo of a larger BRAIN INITIATIVE-funded project in Kriegstein lab to understand the thousands of different cell types that occupy the developing human brain t the moment
and the Damon Runyon Cancer Research Foundation e
#Gene Test Finds Which Breast cancer Patients Can Skip Chemo Many women with early-stage breast cancer can skip chemotherapy without hurting their odds of beating the disease-good news from a major study that shows
the value of a gene-activity test to gauge each patient's risk. The test accurately identified a group of women
whose cancers are so likely to respond to hormone-blocking drugs that adding chemo would do little
if any good while exposing them to side effects and other health risks. In the study, women who skipped chemo based on the test had less than a 1 percent chance of cancer recurring far away
such as the liver or lungs, within the next five years.""You can't do better than that,
"said the study leader, Dr. Joseph Sparano of Montefiore Medical center in New york. An independent expert, Dr. Clifford Hudis of New york's Memorial Sloan Kettering Cancer Center, agreed."
The study was sponsored by the National Cancer Institute. Results were published online Monday by the New england Journal of Medicine
and discussed at the European Cancer Congress in Vienna. The study involved the most common type of breast cancer-early stage, without spread to lymph nodes;
hormone-positive, meaning the tumor's growth is fueled by estrogen or progesterone; and not the type that the drug Herceptin targets.
Each year, more than 100,000 women in the United states alone are diagnosed with this. The usual treatment is followed surgery by years of a hormone-blocking drug.
But many women also are urged to have chemo, to help kill any stray cancer cells that may have spread beyond the breast
and could seed a new cancer later. Doctors know that most of these women don't need chemo
but there are no great ways to tell who can safely skip it. A California company, Genomic Health Inc.
and others that indicate a likely response to hormone therapy treatment. Past studies have looked at how women classified as low,
Women in the middle group were assigned randomly to get hormone therapy alone or to add chemo. Results on these groups are not yet ready-the study is continuing.
But independent monitors recommended the results on the low-risk group be released, because it was clear that adding chemo would not improve their fate.
About 94 percent were free of any invasive cancer, including new cancers at other sites or in the opposite breast."
"These patients who had low risk scores by Oncotype did extraordinarily well at five years,
"said Dr. Hope Rugo, a breast cancer specialist at the University of California, San francisco, with no role in the study."
"Dr. Karen Beckerman, a New york city obstetrician diagnosed with breast cancer in 2011, said she was advised to have feared chemo
A doctor suggested the gene test and she scored very low for recurrence risk.""I was convinced that there was no indication for chemotherapy.
Mary Lou Smith, a breast cancer survivor and advocate who helped design the trial for ECOG, the Eastern Cooperative Oncology Group,
which Medicare and many insurers cover. Others besides Oncotype DX also are on the market,
to compete on price and accuracy.""The future is bright"for gene tests to more precisely guide treatment,
First, it expands our knowledge of the biological role of Vitamin b12, which was understood already to help convert fat into energy,
and to be involved in brain formation, but has now been identified as a key part of photoreceptor proteins the structures that allow organisms to sense
and made it a light sensor, said Catherine Drennan, a professor of chemistry and biology at MIT.
The findings are detailed this week in the journal Nature. The paper describes the photoreceptors in three different states:
to understand how it works at each stage, Drennan said. The paper has nine co-authors,
graduate students Percival Yang-Ting Chen, Marco Jost, and Gyunghoon Kang of MIT; Jesus Fernandez-Zapata and S. Padmanabhan of the Institute of Physical chemistry Rocasolano, in Madrid;
and Maria Carmen Polanco, of the University of Murcia, in Murcia, Spain. The researchers used a combination of X-ray crystallography techniques
and in-vitro analysis to study the bacteria. Drennan, who has studied enzymes that employ Vitamin b12
since she was a graduate student, emphasizes that key elements of the research were performed by all the co-authors.
Jost performed crystallography to establish the shapes of the structures, while the Spanish researchers, Drennan notes, id all of the control experiments to show that we were really thinking about this right,
of which exactly three are bound to the genetic material something Drennan said surprised her. hat the best part about science,
said Rowena Matthews, a professor emerita of biological chemistry at the University of Michigan, who has read the paper.
#Pseudo-platelet Drug Delivery System Targets Cancer Researchers are using patients own platelet membranes to coat drugs and use as nanovehicles for anticancer treatments.
A paper published online Sept. 29 in Advanced Materials outlines the work successfully done in animal models.
Corresponding author Zhen Gu, an assistant professor in the joint biomedical engineering program at North carolina State university and the University of North carolina Chapel hill, said there are two significant benefits in using platelet membranes to coat anticancer drugs.
comparted to about six hours for nanoscale vehicles without the coating. his combination of features means that the drugs can
not only attack the main tumor site, but are more likely to find and attach themselves to tumor cells circulating in the bloodstream essentially attacking new tumors before they start,
said Quanyin Hu, lead author of the paper and a Ph d. student in the joint biomedical engineering program.
The process works by isolating platelets from a blood sample then extracting platelet membranes which are placed then in a solution with a nanoscale gel containing the anticancer drug doxorubicin (Dox).
Dox attacks the nucleus of a cancer cell. Compacting the solution forces the gel through the membranes
and creates nanoscale spheres that consist of platelet membranes with Dox-gel cores. The surface of the spheres are coated then with the anticancer drug TRAIL,
which attacks the cell membrane of cancer cells. Studies on mice found that using the combination drug delivery system in the form of a pseudo-platelet was significantly more effective against large tumors
and circulating tumor cells than using the drugs in a nanogel delivery system without the platelet membrane. e like to do additional preclinical testing on this technique,
Gu said. nd we think it could be used to deliver other drugs, such as those targeting cardiovascular diseases, in
which the platelet membrane could help us target relevant sites in the body. i
#An Accessible Approach to Making a Mini-brain If you need a working miniature brain say for drug testing, to test neural tissue transplants,
or to experiment with how stem cells work a new paper describes how to build one with
what the Brown University authors say is relative ease and low expense. The little balls of brain aren performing any cogitation,
but they produce electrical signals and form their own neural connections synapses making them readily producible testbeds for neuroscience research,
said graduate student Molly Boutin, co-lead author of the new paper in the journal Tissue Engineering:
Part C. lot of the work that done right now is in two-dimensional culture, but this is an alternative that is much more relevant to the in vivo living scenario.
She compared them to retail 3-D printers which have proliferated in recent years, bringing that once-rare technology to more of a mass market. e could allow all kinds of labs to do this research.
and have formed complex 3-D neural networks within two to three weeks, the paper shows. 25-cent mini-brains There are fixed costs, of course,
said study senior author Diane Hoffman-Kim, associate professor of molecular pharmacology, physiology and biotechnology and associate professor of engineering at Brown. e knew it was a relatively high-throughput system,
but even we were surprised at the low cost per mini-brain when we computed it, Hoffman-Kim said.
Hoffman-Kim lab collaborated with fellow biologists and bioengineers at Brown faculty colleagues Julie Kauer, Jeffrey Morgan
She wanted to develop a testbed for her lab basic biomedical research. She was interested, for example,
as has been proposed to treat Parkinson disease. Boutin was interested in building working 3-D cell cultures to study how adult neural stem cells develop.
Morgan Providence startup company, Microtissues Inc.,makes the 3-D tissue engineering molds used in the study.
Cells connect and communicate within a realistic geometry, rather than merely across a flat plane as in a 2-D culture.
-Longevity: In testing, cultured tissues live for at least a month. Hoffman-Kim, who is affiliated with the Brown Institute for Brain science
and the Center for Biomedical engineering, said she hopes the mini-brains might proliferate to many different labs,
we think you shouldn have to equip yourself with a microelectronics facility, and you shouldn have to do embryonic dissections
#Identifying Cancer's Food Sensors May Help Halt Tumor Growth Oxford university researchers have identified a protein used by tumors to help them detect food supplies.
A team from Oxford university's Department of Physiology, Anatomy and Genetics led by Dr. Deborah Goberdhan worked with cancer doctor and researcher, Professor Adrian Harris,
and acquire nutrients is critical for a cancer to grow. Dr. Goberdhan's and Prof Harris's groups collaborated to develop an antibody that could be used to highlight PAT4 in human tissue samples.
This was used then to study anonymous tumor samples taken from patients with colorectal cancer, a common form of the disease.
The results were compared to the known outcomes for the patients. Those who had higher levels of PAT4 in their tumors did less well than those with lower levels-being more likely to relapse and die.
The researchers then looked at what happened when PAT4 levels were reduced. They showed that by reducing PAT4 levels,
cancerous tumors grew more slowly. Dr. Goberdhan said:''These findings support each other. Not only do higher levels of PAT4 mean a worse outcome,
'The research, funded by Cancer Research UK, the Wellcome Trust and the Biotechnology and Biological sciences Research Council will be published in the science journal Oncogene on 5 october 2015.
It continues and may eventually provide a way of increasing survival from cancer r
#Scientists Grow Old Brain cells from Patientsskin Cells Researchers from the Salk Institute for Biological Studies have found a way to create aged brain cells from patientsskin samples for the first time.
Fibroblasts, which are cells in connective tissue, from older people are converted directly into induced neurons. his lets us keep age-related signatures in the cells
so that we can more easily study the effects of aging on the brain, said study author Rusty Gage, a professor in the Salk Institute Laboratory of Genetics.
Researchers believe this technique will be very helpful to scientists studying age-related diseases such as Parkinson and Alzheimer.
The paper was published Oct 8 in Cell Stem Cell. In an older approach, skin cells were taken and turned into induced pluripotent stem cells,
which could then be turned into any cell in the body, such as brain cells, for further study.
However, this technique did not guarantee cells with epigenetic signatures of older cells. This made it difficult to study the aging of the human brain
because researchers couldn create aged brain cells. s researchers starting using these cells more, it became clear that during the process of reprogramming to create stem cells the cell was rejuvenated also in other ways,
said author Jerome Mertens, a postdoctoral research fellow. The team attempted a new technique, and showed that it possible to directly convert skin cells to neurons,
After, they compared the patterns of gene expression in the resulting neurons with cells taken from autopsied brains.
Different patterns of gene expression were recognizable using the direct conversion method, depending on the age of the person they were created from. he neurons we derived showed differences depending on donor age,
said Mertens. nd they actually show changes in gene expression that have been implicated previously in brain aging.
which plays a role in neurodegenerative diseases, were lower in neurons derived from older patients.
but as of now the work only tested the effectiveness in creating brain cells i
#RNA Editing Technique Treats Severe Form of Muscular dystrophy An RNA editing technique called xon skippinghas shown preliminary success in treating a rare and severe form of muscular dystrophy that currently has no treatment
, based on a new study from Northwestern Medicine and the University of Chicago. Children with the disease lose significant muscle strength early in life.
The discovery stems from the persistence of a father--Scott Frewing --whose two sons were diagnosed with a rare and severe form of muscular dystrophy
and his search for and partnership with the genetic scientist--Dr. Elizabeth Mcnally--who studies the disease.
The rare form of the disease is Limb Girdle Muscular dystrophy Type 2c. Mcnally is director of the Center for Genetic Medicine at Northwestern University Feinberg School of medicine and the former director of the Institute of Cardiovascular Research at UCHICAGO,
which is where she began the research. She also is a physician at Northwestern Medicine.
The new therapy has been licensed to the Kurt+Peter Foundation, which supports Limb Girdle Muscular dystrophy 2c research
and is being developed with the goal of clinical trials and eventual commercial treatments. The boysfamily and friends started the foundation in 2010 to apply promising research to Limb Girdle Muscular dystrophy Type 2c.
The finding was published Oct 12 in the Journal of Clinical Investigation. Originally developed to treat Duchenne Muscular dystrophy
another form of muscle disease, exon skipping coaxes cells to kipover abnormal sections of the genetic code,
so that the body can make a functional protein, which in this case, governs muscle function and development.
In the paper, lead investigator Mcnally summarizes her research in fruit flies and mouse models. Her team,
which included Quan Gao a University of Chicago graduate student and Dr. Eugene Wyatt, a postdoctoral fellow at Northwestern, demonstrated that protein made from exon skipping was functional to stabilize and slow progress of the disease.
Working with human cells obtained from individuals with the disease the team showed that exon skipping can be induced successfully with antisense compounds. e recognize that this is version 1. 0,
Mcnally said. ut if this can stabilize individuals with this disease, even if it gave them 10 more years of walking, that huge.
That would also mean 20 to 30 more years of breathing, and that is hugely beneficial for the patients and for their parents who are caring for them.
And, of course, wee interested in developing version 2. 0 that will be even better. Limb Girdle Muscular dystrophy is caused by mutations in any of at least 15 different genes
and affects 1 in 14, 500 to 1 in 123,000 annually. Individuals with Limb Girdle Muscular dystrophy Type 2c have detrimental mutations in a key protein, gamma sarcoglycan,
which is necessary for normal muscle development and function. The disease is an inherited disorder that is found in patients around the world
and is prevalent in France, northern Africa and parts of South america. Although children with the disease are able to live normally at young ages,
over time their deteriorating muscles prevent them from engaging in a number of typical childhood activities.
Many of the children with the disease are in a wheelchair in their mid-to-late teenage years.
Scott Frewing sons Kurt and Peter, were diagnosed with the disease in 2009 and 2010 respectively.
The boysfamily and friends started the Kurt+Peter Foundation in 2010 to apply promising research to Limb Girdle Muscular dystrophy Type 2c.
In 2010, Frewing, president of the Kurt+Peter Foundation, began proactively looking for scientists researching Limb Girdle Muscular dystrophy Type 2c and similar forms of muscular dystrophy,
with hope of supporting research to find a treatment. When Frewing approached Mcnally in 2010,
she was one of the only researchers worldwide working on the disease. Frewing had heard of exon skipping
Mcnally didn think that exon skipping would make the tiny relevant protein in the disease functional.
and development of this potential therapy. here are always new ways to treat a disease,
Mcnally said. his partnership is a perfect example of how precision medicine can help address very rare diseases.
A new partnership among the University of Chicago Northwestern University and The Kurt+Peter Foundation will support the development of therapies for Limb Girdle Muscular dystrophy Type 2c.
The Kurt+Peter Foundation is licensing Mcnally research and hopes to turn her discoveries in the laboratory into treatments that could help to slow the decline in muscle function.
The Foundation will continue to partner with Mcnally to further test exon skipping in Limb Girdle Muscular dystrophy Type 2c
and develop the therapy. Mcnally and Frewing are looking to clear the hurdles necessary to begin clinical trials.
the molecules that function to regulate gene expression that are necessary to make the treatment. e are thrilled to be able to continue development of this promising treatment technique,
"This is a terrible disease affecting children worldwide, and we hope to soon be able to provide families with treatment techniques that can lessen the disease severity.
The agreement among the Kurt+Peter Foundation, UCHICAGO and Northwestern is the first license UCHICAGO has executed with a foundation. his arrangement is a great example of how research institutions
and resources to the table and work together to develop new therapeutics for small groups of patients,
said Thelma Tennant, assistant director at UCHICAGOTECH, the University of Chicago Center for Technology Development & Ventures,
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