#New Protein Manufacturing Process Unveiled Researchers from Northwestern University and Yale university have developed a user friendly technology to help scientists understand how proteins work
Such knowledge could pave the way for new drugs for a myriad of diseases, including cancer.
The human body has a nifty way of turning its proteins on and off to alter their function and activity in cells:
however, about how this dynamic process works in humans. Using a special strain of E coli bacteria,
and structure of phosphoproteins and identify which ones are involved in disease. his innovation will help advance the understanding of human biochemistry and physiology,
a biochemical engineer who led the Northwestern team. The study was published Sept. 9 by the journal Nature Communications.
Trouble in the phosphorylation process can be a hallmark of disease, such as cancer, inflammation and Alzheimer disease.
The human proteome (the entire set of expressed proteins) is estimated to be phosphorylated at more than 100,000 unique sites,
and their role in disease a daunting task. ur technology begins to make this a tractable problem,
Jewett, associate professor of chemical and biological engineering at Northwestern Mccormick School of engineering, and his team worked with Yale colleagues led by Jesse Rinehart.
As a synthetic biologist, Jewett uses cell-free systems to create new therapies, chemicals and novel materials to impact public health
and the environment. his work addresses the broader question of how can we repurpose the protein synthesis machinery of the cell for synthetic biology,
Jewett said. ere we are finding new ways to leverage this machinery to understand fundamental biological questions, specifically protein phosphorylation.
Jewett and his colleagues combined state-of-the-art genome engineering tools and engineered biological artsinto a lug-and-playprotein expression platform that is cell-free.
Cell-free systems activate complex biological systems without using living intact cells. Crude cell lysates, or extracts, are employed instead.
Specifically, the researchers prepared cell lysates of genomically recoded bacteria that incorporate amino acids not found in nature.
This allowed them to harness the cell engineered machinery and turn it into a factory
capable of on-demand biomanufacturing new classes of proteins. his manufacturing technology will enable scientists to decrypt the phosphorylation odethat exists in the human proteome,
said Javin P. Oza, the lead author of the study and a postdoctoral fellow in Jewett lab. To demonstrate their cell-free platform technology,
the researchers produced a human kinase that is involved in tumor cell proliferation and showed that it was functional and active.
Kinases are implicated in many diseases and therefore, of particular interest. he ability to produce kinases for study should be useful in learning how these proteins function and in developing new types of drugs,
Jewett said. The National institutes of health, the Defense Advanced Research Projects Agency and the David and Lucille Packard Foundation Fellowship supported the research.
#SAM-Screener Epigenetic Methylation Test The United states Patent and Trademark Office has issued a patent to Cayman Chemical
and the University of Michigan claiming novel reagents used for screening small-molecule chemical libraries for new drug leads.
The reagents are fluorescent detection analytes that competitively bind to a key cofactor binding site of enzymes that catalyze methylation of histones, DNA, and RNA.
These epigenetic modifications regulate gene expression, impacting normal growth as well as cancer and disease. Dysregulation of histone methylation patterns is observed in a variety of human cancers, inflammation,
and neurodegenerative diseases, validating histone methyltransferases (HMTS) as an important class of drug targets among biomedical researchers.
The newly issued patent US No. 9, 120,820, claims detection analyte probes based on a natural product mimic of the methyltransferase cofactor S-adenosylmethionine (SAM.
Aptly named SAM-Screener, these probes are the foundation of Cayman high-throughput, one-step florescent binding assays for identification of SAM-competitive methyltransferase inhibitors from small-molecule chemical libraries. he SAM-Screener technology meets the currently unaddressed need for rapid and efficient
Custom assay development to adapt this assay format to other HMTS is also available through Cayman epigenetic screening
Cayman is poised to expand on the technology with a patent pending second-generation SAM mimic-based probe designed to competitively bind to SAM-binding sites of a different set of methyltransferases.
This probe will enable the screening of chemical libraries against a broader panel of target methyltransferase enzymes e
Engineers from the University of Bradford and a UK company called Sofmat developed the barcode,
An estimated 10 to 30 percent of global medicines sold in developing countries like Afghanistan
and parts of Africa are counterfeit, according to The Centers for Disease Control and Prevention (CDC).
During the manufacturing process, each individual tablet would be imprinted with tiny pinpricks, reports The Guardian.
Medical professionals would then be able to check these small notches with a scanner before they give the medication to a patient.
#Lab-on-a-chip Cuts Costs of Sophisticated Lab Tests Engineers at Rutgers University have designed a three-inch long,
The new device uses microfluidics technology and could significantly reduce the cost of sophisticated tests for diseases such as HIV, Lyme disease and syphilis, according to the study authors.
who now works in biopharmaceutical research and development at Glaxosmithkline, published their results in the journal Lab on a Chip in addition to being able to use less fluid,
Ghodbane advisor, Martin Yarmush, the Paul and Mary Monroe Chair and Distinguished Professor of biomedical engineering at Rutgers, said the results are as accurate and sensitive as the standard benchtop assay. ith our technology,
The ability to analyze miniscule amounts of fluid could also promote more research on autoimmune joint diseases,
#New Leukemia Gene Stops Blood cells rowing Upuniversity of Manchester scientists have identified a gene FOXC1 that,
if switched on, causes more aggressive cancer in a fifth of acute myeloid leukemia (AML) patients, according to a Cancer Research UK study published in the journal Cancer cell.
The FOXC1 gene is switched normally on during embryonic development and is needed to turn cells into specialised tissues,
But this new research found that in certain patients with AML a type of blood cancer that affects white blood cells
This triggers the cancer to be more aggressive, as young cells are able to replicate more than mature cells causing cancer cells to grow faster
Of these, around 20 percent would have had the FOXC1 gene wrongly switched on in their cancer.
Dr. Tim Somervaille, lead author from the Cancer Research UK Manchester Institute at The University of Manchester,
which makes the cancer grow more rapidly. here are certain situations where this gene is necessary,
Nell Barrie, senior science communication manager at Cancer Research UK said: t essential that we continue to research basic biology to further understand how cells become cancerous.
In this study, identifying a specific gene behind more aggressive forms of acute myeloid leukaemia could give clues for new ways to personalise treatments for select patients.
The better we understand the nuts and bolts of each cancer, the sooner we can find new ways to stop it.
This study was funded by Cancer Research UK with additional funding from the charity Bloodwise which recently changed its name from Leukaemia & Lymphoma Research a
#chillesheelof Sickle cell Disease? Researchers from Dana-Farber/Boston Children Cancer and Blood disorders Center have found that changes to a small stretch of DNA may circumvent the genetic defect behind sickle cell disease.
The discovery, outlined in the journal Nature, opens a promising path for developing gene-editing approaches to treat the disease and other hemoglobin disorders.
This stretch of DNA, called an enhancer, controls a molecular switch that determines whether a red blood cell produces the adult form of hemoglobin
which in sickle cell disease is mutated or a fetal form that is unaffected by and counteracts the effects of the mutation.
Other studies have indicated that sickle-cell patients with elevated levels of fetal hemoglobin have a milder form of the disease.
The new study was led by Stuart Orkin of Dana-Farber/Boston Children, who is also David G. Nathan Professor of Pediatrics at Harvard Medical school (HMS);
Daniel Bauer, also of Dana-Farber/Boston Children and an assistant professor of pediatrics at HMS;
and Feng Zhang of the Broad Institute of MIT and Harvard. The research was spurred by the discovery that naturally occurring beneficial variations in the DNA sequence in this enhancer dial down the molecular switch only in red blood cells.
To mimic and improve upon the effects of these variations, the research team used recently developed gene-editing tools to cut out tiny sections of DNA step by step along the entire length of the enhancer in blood stem cells from human donors.
a pediatric hematologist/oncologist at Dana-Farber/Boston Children. ur goal was to break the enhancer,
rather than fix the hemoglobin mutation, but to do so in very precise ways that are only possible
when the journal Science published their report of the discovery of the enhancer that directs expression of BCL11A only in red blood cells. ee now targeted the modifier of the modifier of a disease-causing gene,
a leader of Dana-Farber/Boston Children who serves as chairman of pediatric oncology at the Dana-Farber Cancer Institute
and associate chief of hematology/oncology at Boston Children Hospital. t a very different approach to treating disease. he data provide proof of principle that targeted edits to BCL11A enhancer in blood stem cells could be an attractive approach
for curing sickle cell disease and related conditions. hese experiments may have revealed the genetic Achillesheel of sickle cell disease,
said Orkin. lterations to these specific portions of the enhancer have the same effect as knocking the whole enhancer out altogether,
suggesting that this could be a promising strategy to translate into the clinic.?Although fixing the sickle mutation itself would seem the most straightforward approach,
it turns out that blood stem cells, the ultimate targets for this kind of therapy, are much more resistant to genetic repair than to genetic disruption, Bauer added. herefore,
making a single DNA cut that breaks the enhancer solely in blood stem cells could be a much more feasible strategy. e
#New Nanoparticles Clean the Environment, Drinking water Nanoparticles are between 1 and 100 nanometers in size.
to combat disease, for filtering fresh drinking water, and much more. Now, researchers from MIT and the Federal University of Goias in Brazil have developed a new technique that uses ultraviolet (UV LIGHT to extract man-made pollutants from soil and water.
These pollutants, including pesticides and endocrine disruptors like bisphenol A, fight hard against natural degradation
and disrupt systems in mammals and other animals. With the help of nanoparticles and UV LIGHT
removal of these toxins could be less expensive and time-consuming than current methods. Lead author Nicolas Bertrand, a former professor at MIT Koch Institute for Integrative Cancer Research, told Laboutlook that he
and colleagues stumbled upon the idea of using UV LIGHT while they were initially designing photosensitive polymers for drug delivery applications.
Once they came up with a polymer that responded to UV LIGHT, they realized that this did not permeate well through skin
and could cause damage to healthy cells. e therefore asked ourselves in which infrastructures UV LIGHT was used already,
How it works The nanoparticles are prepared from molecules (synthetic macromolecules commonly called plastics) that have a protective,
hydrophilic (water-loving) shell and a hydrophobic (water-fearing) spherical core. he polymers are synthetized to ensure that
When this happens on a nanoparticle, its protecting corona is removed and only the hydrophobic core remains.
These akedhydrophobic plastic beads are stabilized not anymore and therefore clump together to minimize contacts with water,
with more than 95 percent of the nanoparticles removed from the water. When the nanoparticle loses its protective layer,
polymers are released into the water. While the polymer released (polyethylene glycol) is recognized as safe and used in various food, pharmaceutical and cosmetics products,
it would be ideal if no material was released or if it could be used by parts of the ecosystem to further minimize environmental impact.
Still, even with the small amount of material released into the water Bertrand nanoparticles have compared benefits with current purification processes.
Some current techniques rely on chemical degradation of pollutants, which can potentially result in toxic by-products.
Plus, these chemical degradation processes do not work on all types of chemicals. hen unusual/unheard of molecules are found as contaminants (for example, the chemical spill in Elk River, WV, in January 2014),
no data exist on the ability of these oxidizing agents to destroy the dangerous chemical, so their value is said questionable,
Bertrand. ince it relies on nonspecific absorption, our approach might be more versatile. Additionally other processes, such as activated carbon extraction, require great energy to push large quantities of water through filters. n our technology,
the nanoparticles float passively in the fluid until we precipitate them. Current water purification infrastructures have UV irradiation systems optimized to kill bacteria,
this irradiation is more than sufficient to precipitate our nanoparticles, Bertrand explained. Bertrand told Laboutlook that one fundamental observation from this work is that small molecules passively absorb on the surface of the nanoparticle,
and that the amounts absorbed correlate with the surface-to-volume ratio, meaning more absorption occurs on small nanoparticles. his is an important consideration for drug delivery
because it could explain what happens with nanoparticles with high drug encapsulation and extensive burst release.
Harnessing nanoparticles in Africa Theresa Dankovich uses nanotechnology to purify drinking water in Africa. By filtering water through paper embedded with silver or copper nanoparticles,
99.9 percent water purity is achievable. She calls it he Drinkable Book. Silver nanoparticles eliminate a wide variety of microorganisms,
including bacteria and some viruses . While some silver and copper will seep from the nanoparticle-coated paper,
the amount is said minimal, Dankovich, and is well below limits for metals put in place by the Environmental protection agency and World health organization.
Dankovich nonprofit company page Drinking Paper, works together with the nonprofit WATERISLIFE to produce a book of this nanoparticle-embedded paper,
which is put in a special holding device that water is filtered then through. One page can filter 26 gallons of drinking water;
one book can filter a person water needs for four years. Dankovich presented her technology
along with results of recent field tests conducted in Africa and Bangladesh at the American Chemical Society (ACS) National Meeting earlier this month.
Drug delivery and beyond The power of nanoparticles is also being harnessed to fight life-threatening lung diseases, such as cystic fibrosis.
Researchers at Johns hopkins university School of medicine, Johns hopkins university Department of Chemical and Biomolecular engineering and Federal University of Rio de janeiro in Brazil conducted a proof-of-concept study that found DNA-loaded nanoparticles could successfully pass through the hard-to-breach mucus barrier
that covers conducting airways of lung-tissue. The mucus barrierhich serves as a protector from foreign materials
and bacterianfortunately prevents targeted therapies from reaching the lungs. Other attempts to penetrate the barrier with nanoparticles were unsuccessful
because they possessed a positive charge that caused them to be tickyand adhere to the negatively charged mucus covering the airways.
To circumvent this problem the team developed a simple method to densely coat the nanoparticles with a nonsticky polymer called PEG,
neutralized the charge and created a non-sticky exterior. Published in the Proceedings of the National Academy of Sciences, the proof-of-concept animal study demonstrates that placing corrective replacement genes
or drugs inside a man-made biodegradable nanoparticle rapperthat patients inhale could penetrate the mucus barrier
a biomedical engineer and faculty member at the Center for Nanomedicine at the Wilmer Eye Institute at Johns Hopkins. Researchers funded by the National Institute of Biomedical Imaging and Bioengineering meanwhile,
stopped brain cancer in rats by delivering gene therapy through nanoparticles. The nanoparticles deliver genes for an enzyme that converts a prodrug called ganciclovir into a glioma cell killer.
There is no reliable treatment for glioma which has a 5-year survival rate of 12 percent.
As in cystic fibrosis, a current delivery method of gene therapy relies on using a virus, which can pose significant safety risks.
Challenges remain Bertrand and other lead author Ferdinand Brandl both left MIT to join pharmacy schools in Quebec city, Canada and Regensburg, Germany, respectively.
Although their nanoparticle technology is solid, some challenges remain before it can be implemented in an industrial application.
As a next step, Bertrand said it would be interesting to design a system where no polymer is released,
Work could also be done to improve the ability to remove increasing amounts of pollutants h
#Personalized Heart Models for Surgical Planning Researchers at MIT and Boston Children Hospital have developed a system that can take MRI scans of a patient heart and,
physical model that surgeons can use to plan surgery. The models could provide a more intuitive way for surgeons to assess
and prepare for the anatomical idiosyncrasies of individual patients. ur collaborators are convinced that this will make a difference,
said Polina Golland, a professor of electrical engineering and computer science at MIT, who led the project. he phrase I heard is that urgeons see with their hands,
This fall, seven cardiac surgeons at Boston Children Hospital will participate in a study intended to evaluate the modelsusefulness.
Golland and her colleagues will describe their new system at the International Conference on Medical Image Computing and Computer Assisted Intervention in October.
Danielle Pace, an MIT graduate student in electrical engineering and computer science, is first author on the paper
and spearheaded the development of the software that analyzes the MRI scans. Medhi Moghari, a physicist at Boston Children Hospital, developed new procedures that increase the precision of MRI scans tenfold
and Andrew Powell, a cardiologist at the hospital, leads the project clinical work. The work was funded by both Boston Children Hospital and by Harvard Catalyst,
a consortium aimed at rapidly moving scientific innovation into the clinic. MRI data consist of a series of cross sections of a three-dimensional object.
Like a black-and-white photograph, each cross section has regions of dark and light, and the boundaries between those regions may indicate the edges of anatomical structures.
Then again, they may not. Determining the boundaries between distinct objects in an image is one of the central problems in computer vision
known as mage segmentation. But general-purpose image-segmentation algorithms aren reliable enough to produce the very precise models that surgical planning requires.
Human factors Typically, the way to make an image-segmentation algorithm more precise is to augment it with a generic model of the object to be segmented.
Human hearts, for instance, have chambers and blood vessels that are usually in roughly the same places relative to each other.
That anatomical consistency could give a segmentation algorithm a way to weed out improbable conclusions about object boundaries.
The problem with that approach is that many of the cardiac patients at Boston Children Hospital require surgery precisely
because the anatomy of their hearts is irregular. Inferences from a generic model could obscure the very features that matter most to the surgeon.
In the past, researchers have produced printable models of the heart by manually indicating boundaries in MRI scans.
Pace and Golland solution was to ask a human expert to identify boundaries in a few of the cross sections
and allow algorithms to take over from there. Their strongest results came when they asked the expert to segment only a small patch ne-ninth of the total area of each cross section.
In that case, segmenting just 14 patches and letting the algorithm infer the rest yielded 90 percent agreement with expert segmentation of the entire collection of 200 cross sections.
Human segmentation of just three patches yielded 80 percent agreement. think that if somebody told me that I could segment the whole heart from eight slices out of 200,
Prognosis Currently, the algorithm examines patches of unsegmented cross sections and looks for similar features in the nearest segmented cross sections.
This and other variations on the algorithm are the subject of ongoing research. The clinical study in the fall will involve MRIS from 10 patients who have received already treatment at Boston Children Hospital.
Each of seven surgeons will be given data on all 10 patients some probably, more than once. That data will include the raw MRI scans and, on a randomized basis,
either a physical model or a computerized 3-D model, based, again at random, on either human segmentations or algorithmic segmentations.
Using that data, the surgeons will draw up surgical plans, which will be compared with documentation of the interventions that were performed on each of the patients.
The hope is that the study will shed light on whether 3-D-printed physical models can actually improve surgical outcomes. bsolutely,
a 3-D model would indeed help, said Sitaram Emani, a cardiac surgeon at Boston Children Hospital who is not a co-author on the new paper. e have used this type of model in a few patients,
and in fact performed irtual surgeryon the heart to simulate real conditions. Doing this really helped with the real surgery in terms of reducing the amount of time spent examining the heart
and performing the repair. think having this will also reduce the incidence of residual lesions imperfections in repair by allowing us to simulate
and plan the size and shape of patches to be used, Emani adds. ltimately, 3d printed patches based upon the model will allow us to tailor prosthesis to patient. inally,
having this immensely simplifies discussions with families, who find the anatomy confusing, Emani said. his gives them a better visual,
and many patients and families have commented on how this empowers them to understand their condition better. e
Now, University at Buffalo researchers and their colleagues at other institutions are publishing a paper online in Nature Communications on Sept. 18 about a new method they developed to more precisely capture how brain cells interact.
The work was led by scientists at UB Hunter James Kelly Research Institute (HJKRI) who conduct research to better understand myelin,
The institute, part of UB New york state Center of Excellence in Bioinformatics and Life sciences, was established in 1997 by Buffalo bills Hall of fame quarterback Jim Kelly
He died in 2005 at the age of 8. The researchers explained that cellular interactions that trigger the production of myelin are especially hard to pinpoint.
explained M. Laura Feltri, M d.,senior author on the paper and an HJKRI researcher and professor of biochemistry and neurology in the Jacobs School of medicine and Biomedical sciences at UB. o study myelin,
And studying this interface is critical in certain diseases she added. n Krabbe, for example, the problem is not just that there isn sufficient myelin,
The new technique for achieving this involves using the second cell (the neuron) as a trigger to attract the first cell (the glial cell.
The discovery will help improve the understanding of and development of new treatments for myelin diseases.
Feltri explained. t provides a glimpse into the social life of cells. his work has important implications for diseases of myelin such as Krabbe disease,
and other neurodegenerative diseases, because the communication between glial cells and neurons is vital for neuroprotection,
extending far away from the glial cell. his has profound implications for glial disease like Krabbe, Charcot-Marie Tooth, peripheral neuropathies or Multiple sclerosis,
said Poitelon. imilarly, neurodegenerative diseases like Huntington disease or Lou Gehrig's, that were considered uniquely diseases of neurons in the past,
are considered now diseases of cellular communications between neurons and glial cells. The work was funded by the National institutes of health o
#Down syndrome Research Untangles Therapeutic Possibilities for Alzheimer More than five million Americans are living with Alzheimer disease (AD.
Of them, 400,000 also have Down syndrome. Both groups have similar looking brains with higher levels of the protein beta amyloid.
In fact, patients with Down syndrome develop the abnormal protein at twice the rate. Results of a pilot study, published in the September issue of Frontiers in Behavioral neuroscience, confirms the pathogenic role of beta amyloid in dementia as seen in both AD
and Down syndrome. eople with Down syndrome represent the world largest population of predetermined Alzheimer disease. By studying these individuals,
we can develop insights into how Alzheimer disease naturally progresses and potential drug targets, said principal investigator Michael Rafii, M d.,Ph d.,assistant professor of neurosciences and interim co-director of the Alzheimer Disease Cooperative Study (ADCS) at UC San diego. The 3-year study
, called The down Syndrome Biomarker Initiative (DSBI), involved twelve participants between the ages of 30 and 60 with Down syndrome,
to study their aging process. The study focused on how soon protein plaques developed, where in the brain they were located and the effects of the plaques on cognition.
To quantify how much amyloid was present in the brain, the study included extensive neuroimaging such as volumetric MRI
amyloid PET, FDG PET, and retinal amyloid imaging. his study shows some of the earliest known Alzheimer disease biomarker changes in adults with Down syndrome
and underscores the need for additional studies, said Rafii. his study will set the stage for the first clinical trial of anti-beta amyloid therapy in the preclinical treatment of Alzheimer disease in adults with Down syndrome.
AD is believed to occur from the toxic buildup of beta amyloid. There are many forms of AD that are inherited genetically,
including Down syndrome. People with Down syndrome have an extra copy of the 21st chromosome where the production gene for the beta amyloid protein resides.
The ADCS was founded by the late Leon Thal M d.,a world leader in Alzheimer research, to promote the discovery, development and testing of new drugs for the treatment of AD.
It is part of a larger AD research and treatment effort at UC San diego, which includes the Shiley-Marcos Alzheimer Disease Research center, under the direction of Douglas Galasko, M d,
. and Edward Koo, M d, . and the Memory Disorders Clinic, headed by Rafii. Studies of AD and other neurodegenerative disorders at UC San diego are part of the clinical
and bench strength of the UC System. In the past five years more than 130 UC investigators have conducted 350 research projects in the AD field, receiving roughly $339 million in funding support for both basic research and clinical trials.
Funding support for this research came, in part, from Janssen Research and development, LLC and the National institutes of health t
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