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Ferritin Cage Enzyme Encapsulation as a New Platform for Nanotechnology

 Reporter: Irina Robu, PhD

In bionanotechnology, biological systems such as viruses, protein complexes, lipid vesicles and artificial cells, are being developed for applications in medicine and materials science.  However, the paper published by Stephan Tetter and Donald Hilvert in Angewandte Chemie International Edition show that it is possible to encapsulate proteins such as ferritin by manipulating electrostatic interactions with the negatively charged interior of the cage.The primary role of ferritin is to protect cells from the damage caused by the Fenton reaction; where, in oxidizing conditions, free Fe(II) produces harmful reactive oxygen species that can damage the cellular machinery.

The ferritin family proteins are protein nanocages that evolved to safely store iron in an oxidizing world. Since ferritin family proteins are able to mineralize and store metal ions, they have been the focus of much research for the production of metal nanoparticles and as prototypes for semiconductor production. The ferritin cage itself is highly symmetrical, and is made up of 24 subunits arranged in an octahedral symmetry. Ferritins are smaller than other protein used for protein   encapsulation.   Their  outer  diameter is only 12 nm, whereas engineered lumazine synthase variants form cages with diameters ranging from about 20 to 60 nm.The ferritin cage displays remarkable thermal and chemical stability it is likely to modify the surface of the ferritin cage through the addition of peptide and protein tags. These characteristics have made ferritins attractive vectors for the delivery of drug molecules and as scaffolds for vaccine design.

In summary, the paper published in Angewandte Chemie International Edition is the first example of protein incorporation by a ferritin.  Dr. Donald Hilvert and colleagues have shown that AfFtn not only complexes positively charged guest proteins within its naturally negatively charged luminal cavity, but that the in vitro mixing technique can be extended to the encapsulation and protection of other functional  fusion proteins.

Hence, the recent discovery of encapsulated ferritins has identified an exciting new platform for use in bio nanotechnology. The use of synthetic biology tools will allow their rapid implementation in materials science, bio-nanotechnology and medical applications.

SOURCE

https://www.readbyqxmd.com/read/28902449/enzyme-encapsulation-by-a-ferritin-cage

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Development of 3D Human Tissue Models Awarded NIH Grants Worth $15M

Reporter: Irina Robu, PhD

NIH has awarded $15 million for Tissue Chip for Disease Modeling and Efficacy Testing to develop 3D human tissue models. The 3D platforms, also called tissue chips support living cells and human tissues, it mimics the complex biological functions of organs/tissues and at the same time provide a new way to test potential drugs and their effectiveness. The awards will allow scientists to study and understand diseases mechanism and forecast how patients respond and is part of the first phase of a five-year program.  According to NCATS Director, Dr. Christopher P. Austin “these tissue chips to provide more accurate platforms to understand diseases, and to be more predictive of the human response to drugs than current research models, thereby improving the success rate of candidate drugs in human clinical trials”.

The awards will be used to study common and rare diseases including rheumatoid arthritis, influenza A, kidney disease, amyotrophic lateral sclerosis, or ALS, arrhythmogenic cardiomyopathy, and hemorrhagic telangiectasia. Award recipients are Brigham and Women’s Hospital, Cedars-Sinai Medical Center, Columbia University, Duke University, Harvard University, Northwestern University, University of California Davis, University of California Irvine, University of Pittsburgh, University of Rochester, University of Washington Seattle and Vanderbilt University.

SOURCE

https://www.mdtmag.com/news/2017/09/nih-grants-15m-development-3d-human-tissue-models

 

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Brain Surgeons Use 3D printing to Practice

Reporter: Irina Robu, PhD

Mechanical thrombectomy is a hopeful new modality of interventional stroke treatment. The countless devices on the market differ with regard to where they apply force on the thrombus, taking a proximal approach such as aspiration devices or a distal approach such as basket-like devices. In 2012, the Food and Drug Administration (FDA) approved mechanical thrombectomy – using a wire to pull clots out of the brains of stroke victims. At the end of the wire a trap exists which is like a noose that that captures the clot. Considering that the mechanical thrombectomy is a very risky procedure, interventional radiologists and neurosurgeons need to train extensively before they work on a real person.

Because of the procedure is very risky, a UConn Health radiologist and medical physicist made it easier for surgeons to practice first before the actual procedure. The team made a life size model of the arteries that the wire must pass through using brain scans and a 3D printer. The life size model will allow the surgeon to be more confident when guiding the wire and will give them the basic techniques on how to move the catheter. Holding the life size model of arteries, brings home how small they are even in an adult man. According to Dr. Ketan Bulsara, this life size model will be used a training model to learn mechanical thrombectomy and being able to model the tumor in advance could personalize and advance patient care.

SOURCE

https://www.mdtmag.com/news/2017/09/uconn-healths-new-3-d-printed-model-allows-brain-surgeons-practice

 

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Winners of 2017 Blavatnik National Awards for Young Scientists

Reporter: Aviva Lev-Ari, PhD, RN

 

presented by to Life Sciences Laureate

 

NEW YORK – June 27, 2017 – The Blavatnik Family Foundation and the New York Academy of Sciences today announced the 2017 Laureates of the Blavatnik National Awards for Young Scientists. Starting with a pool of 308 nominees – the most promising scientific researchers aged 42 years and younger nominated by America’s top academic and research institutions – a distinguished jury first narrowed their selections to 30 Finalists, and then to three outstanding Laureates, one each from the disciplines of Life Sciences, Chemistry and Physical Sciences & Engineering. Each Laureate will receive $250,000 – the largest unrestricted award of its kind for early career scientists and engineers. This year’s Blavatnik National Laureates are:

  • Feng Zhang, PhD, Core Member, Broad Institute of MIT and Harvard; Associate Professor of Brain and Cognitive Sciences and Biomedical Engineering, MIT; Robertson Investigator, New York Stem Cell Foundation; James and Patricia Poitras ’63 Professor in Neuroscience, McGovern Institute for Brain Research at MIT.Dr. Zhang is being recognized for his role in developing the CRISPR-Cas9 gene-editing system and demonstrating pioneering uses in mammalian cells, and for his development of revolutionary technologies in neuroscience.
  • Melanie S. Sanford, PhD, Moses Gomberg Distinguished University Professor and Arthur F. Thurnau Professor of Chemistry, University of Michigan. Dr. Sanford is being celebrated for developing simpler chemical approaches – with less environmental impact – to the synthesis of molecules that have applications ranging from carbon dioxide recycling to drug discovery.
  • Yi Cui, PhD, Professor of Materials Science and Engineering, Photon Science and Chemistry, Stanford University and SLAC National Accelerator Laboratory. Dr. Cui is being honored for his technological innovations in the use of nanomaterials for environmental protection and the development of sustainable energy sources.

“The work of these three brilliant Laureates demonstrates the exceptional science being performed at America’s premiere research institutions and the discoveries that will make the lives of future generations immeasurably better,” said Len Blavatnik, Founder and Chairman of Access Industries, head of the Blavatnik Family Foundation, and an Academy Board Governor.

“Each of our 2017 National Laureates is shifting paradigms in areas that profoundly affect the way we tackle the health of our population and our planet — improved ways to store energy, “greener” drug and fuel production, and novel tools to correct disease-causing genetic mutations,” said Ellis Rubinstein, President and CEO of the Academy and Chair of the Awards’ Scientific Advisory Council. “Recognition programs like the Blavatnik Awards provide incentives and resources for rising stars, and help them to continue their important work. We look forward to learning where their innovations and future discoveries will take us in the years ahead.”

The annual Blavatnik Awards, established in 2007 by the Blavatnik Family Foundation and administered by the New York Academy of Sciences, recognize exceptional young researchers who will drive the next generation of innovation by answering today’s most complex and intriguing scientific questions.

SOURCE

http://blavatnikawards.org/news/items/winners-2017-blavatnik-national-awards-young-scientists-include-pioneering-bioengineer-chemist-and-nanoscientist-will-receive-250000-prizes/

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Novel Blood Substitute – ErythroMer

Reporter: Irina Robu, PhD

For years, scientists have tried ineffectively to create an artificial molecule that emulates the oxygen-carrying function of human red blood cell but the efforts failed because of oxygen delivery and safety issues. Now, a group of researchers led by Dr. Alan Doctor at Washington University in Saint Louis, are trying to resuscitate blood substitutes with a new nanotechnology-based, artificial red blood cell may overcome the problems that killed products designed by a team of companies such as BiopureAlliance PharmaceuticalsNorthfield Labs and even Baxter. Dr. Alan Doctor’s new company, Kalocyte is advancing the development of the

The donut-shaped artificial cells, ErythroMer are one-fiftieth the size of human red blood cells. ErythroMer is a novel blood substitute composed of a patented nanobialys nanoparticle. A special lining and control system tied to changes in blood Ph allows Erythromer to grab onto oxygen in the lungs and then dispense the oxygen in tissues where it is needed. The new artificial cells are intended to sidestep problems with vasoconstriction or narrowing of blood vessels.

Erythromer is stored freeze dried and reconstituted with water when needed but it can also be stored at room temperature which makes it for military and civilian trauma.

Trials have been successful in rats, mice, and rabbits, and human trials are planned. However, moving Erythromer into human clinical trials is still 8-10 years away.

SOURCE

https://www.thestreet.com/story/13913099/1/human-blood-substitutes-once-dead-now-resuscitated.html

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First 3D Printed Tibia Replacement

Reporter: Irina Robu, PhD

Current advances have allowed 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Thanks to 3D printing, an Australian man got to keep his leg. The man, Reuben Lichter nearly lost his leg above the knee due to a bacterial infection. Doctors told him that he had osteomyelitis which infected his entire bone. Lichter’s bacterial disease of osteomyelitis affects 2 in every 10,000 people in the United States. He had two choices: an experimental procedure using the 3D printed bone or lose his leg. For Lichter, the choice was easy.

Michael Wagels who served as the lead surgeon performed the world’s first-ever transplant surgery using a 3D printed bone. The scaffold was initially modeled at Queensland University of Technology. Biomedical engineers designed the scaffold to promote bone growth around it and then slowly dissolve over time. To have the body successfully grow around the scaffold, the team introduced tissue and blood vessels from both of Lichter’s legs to the scaffold. The surgery itself happened over five operations at Brisbane’s Princess Alexandra Hospital.

However, the next major challenge for biomedical engineers is how to successfully 3D print organs.

SOURCE

https://interestingengineering.com/australian-man-gets-worlds-first-3d-printed-tibia-replacement

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Walking DNA Nanorobot

Reporter: Irina Robu, PhD

New research from California Institute of Technology headed by Anupama Thubagere and Lulu Qian built robots from DNA and programmed them to sort and deliver molecules to a specified location. These robots can potentially transform the drug delivery field to how body fights infections to how microscopic measurements are made. The dominant premise of DNA robots is that rather than creating molecular devices from scratch, we can use the power of molecular machinery by building microscopic-size robots and send them to places that are then impossible to reach, such as a cell or a hard-to-reach cancerous tumor. These robots demonstrated the ability to perform simple tasks, however this latest effort ramped up a path by programming DNA robots to perform a cargo‐sorting task and possibly many other tasks.

Each robot was built from a single-stranded DNA molecule of just 53 nucleotides equipped with “legs” for walking and “arms” for picking up objects. The robot are 20 nanometers tall and their walking strides measures six nanometers long, where one nanometer is a billionth of a meter. For the cargo, the researchers used two types of molecules, each being a distinct single-stranded piece of DNA. For the tests, the researchers placed the cargo onto a random location along the surface of a two-dimensional origami DNA test platform. The walking DNA robots moved in parallel along this surface, hunting for their cargo.

To see if a robot successfully picked up and dropped off the right cargo at the right location, the researchers used two fluorescent dyes to differentiate the molecules.

The researchers guess that each DNA robot took around 300 steps to complete its task, or roughly ten times more than in previous efforts. Though, more work is needed to figure out how these DNA robots perform under different environmental conditions. This new study suggests a worthwhile methodology for scientists to continue pursuing.

SOURCE

http://science.sciencemag.org/content/357/6356/eaan6558

 

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