Molecular Robotics at the Wyss Institute

Collaborations between nanotechnologists, synthetic biologists, and computer scientists create nanoscale tools that could revolutionize fields from cancer diagnostics to materials science
By Lindsay Brownell

(BOSTON) — DNA has often been compared to an instruction book that contains the information needed for a living organism to function, its genes made up of sequences of the nucleotides A, G, C, and T echoing the way that words are composed of strings of letters. DNA, however, has several advantages over books as an information-carrying medium, one of which is especially profound: based on its nucleotide sequence alone, single-stranded DNA can self-assemble, or bind to a complementary DNA strand, to form a complete double-stranded helix, without human intervention. That would be like printing the instructions for making a book onto loose pieces of paper, putting them into a box with glue and cardboard, and watching them spontaneously come together to create a book with all the pages in the right order.

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New research ‘Clicks’ biology and nanomaterials together

1 February 2018

Protein connecting two nanocarbons

Research at Cardiff University has built molecular bridges between nano-carbons and proteins that should inspire new approaches to generating bionano-materials.

Collaborative research between the Dafydd Jones group at Cardiff University’s School of Biosciences and Queen Mary University has utilised molecular engineering to address problems in combining nano-carbons and proteins.

Nano-carbon materials, like graphene or carbon nanotubes, are considered to be the next generation of ‘wonder materials’ due to their useful molecular properties which can be valuable for nanotechnology. Similarly, proteins are vital within nature, undertaking all useful processes required for life by acting like nano-machines.

The useful properties of proteins and nano-carbon has led to great effort in marrying their properties together by combining them at a molecular level to generate biohybrid systems.

These new systems have the potential to be used in molecular electronics or health-detecting sensors, however their assembly at a molecular level has proved difficult.

Research by Cardiff University used a process in synthetic biology called Click Chemistry to solve these issues.

Dafydd Jones, Cardiff University School of Biosciences, said: “Building these new systems on a very small scale has its difficulties.

“As these biohybrid systems are entirely new, it is like trying to assemble flat-pack furniture without the instructions – you will get a jumbled product. But our research has been able to address this problem by using principles of molecular engineering.

“By using synthetic biology, we reprogrammed the genetic code for the proteins to allow us to introduce new chemistry, which is not present in nature.

By using this technique, we attached proteins to carbon nanotubes in a one-to-one manner. We used the protein as a molecular bridge, joining together the two nanotubes, using a reaction called Click Chemistry.  Rest

Cancer ‘vaccine’ eliminates tumors in mice

Activating T cells in tumors eliminated even distant metastases in mice, Stanford researchers found. Lymphoma patients are being recruited to test the technique in a clinical trial.

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Man in a lab coat in the foreground with a woman in the background working on a computer

Ronald Levy (left) and Idit Sagiv-Barfi led the work on a possible cancer treatment that involves injecting two immune-stimulating agents directly into solid tumors.
Steve Fisch

Injecting minute amounts of two immune-stimulating agents directly into solid tumors in mice can eliminate all traces of cancer in the animals, including distant, untreated metastases, according to a study by researchers at the Stanford University School of Medicine.

The approach works for many different types of cancers, including those that arise spontaneously, the study found.

The researchers believe the local application of very small amounts of the agents could serve as a rapid and relatively inexpensive cancer therapy that is unlikely to cause the adverse side effects often seen with bodywide immune stimulation.

“When we use these two agents together, we see the elimination of tumors all over the body,” said Ronald Levy, MD, professor of oncology. “This approach bypasses the need to identify tumor-specific immune targets and doesn’t require wholesale activation of the immune system or customization of a patient’s immune cells.”  Rest

A New Day in Cancer Treatment

by Jack D. Hidary

It is time for a complete revolution in how we treat cancer.   The current trifecta of surgery, radiation and chemotherapy has yielded marginal improvements in outcomes, but will not provide long-term positive results for the growing number of cancer cases in society.

The good news is that we have new tools at hand. Each of these needs further development, but this is where we should be focused.  Here are four tools worth spending time and money on to bring to the fore of cancer treatment:

1/ Immunotherapy; 2/ Genomics; 3/ Nanomedicine; and 4/ Machine learning

Full post at https://www.linkedin.com/pulse/new-day-cancer-treatment-jack-hidary/

Scientists use directed evolution to develop better viruslike capsules

Artificial viral capsids that hold their own genomic material could aid drug delivery

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Schematic shows how bacteria produce synthetic capsids from introduced genes.
To produce synthetic capsids, bacteria transcribe two DNA genes (not shown) into one piece of mRNA (bicistronic) and translate the mRNA into proteins, which oligomerize to trimers and pentamers. The oligomers bind their encoding mRNA and self-assemble into capsids that can then be tested in mice.
Credit: Adapted from Nature

Viruses are pretty simple: They’re small DNA or RNA genomes enclosed in protein containers called capsids. Scientists have designed and engineered proteins that self-assemble into viruslike containers that hold cargoes such as drugs, vaccines, and biomolecules.

David Baker of the University of Washington and coworkers have now devised the first so-called nucleocapsids, artificial capsids that enclose their own RNA genomes. The development opens the door for researchers to use directed evolution, a repetitive protein mutation and screening technique, to optimize the properties of these protein containers for drug delivery applications (Nature 2017, DOI: 10.1038/nature25157).

In particular, the team optimized nucleocapsids to remain stable for long times and to protect their RNA cargoes from degradation while floating around in the bloodstreams of mice. The artificial nucleocapsids could be useful for delivering small molecules, biomolecules, or materials for therapeutic or nanomaterials applications. They could even provide housing for future synthetic lifeforms, the researchers say.  Rest

Young Again: How One Cell Turns Back Time

New York Times article summary: With every birth, cells begin anew. Scientists have found a biological mechanism underpinning the process in worms, which one day may be harnessed to restore our own damaged cells.

A lysosomal switch triggers proteostasis renewal in the immortal C. elegans germ lineage (Nature abstract)

Although individuals age and die with time, an animal species can continue indefinitely, because of its immortal germ-cell lineage1. How the germline avoids transmitting damage from one generation to the next remains a fundamental question in biology. Here we identify a lysosomal switch that enhances germline proteostasis before fertilization. We find that Caenorhabditis elegans oocytes whose maturation is arrested by the absence of sperm2 exhibit hallmarks of proteostasis collapse, including protein aggregation. Remarkably, sperm-secreted hormones re-establish oocyte proteostasis once fertilization becomes imminent. Key to this restoration is activation of the vacuolar H+-ATPase (V-ATPase), a proton pump that acidifies lysosomes3. Sperm stimulate V-ATPase activity in oocytes by signalling the degradation of GLD-1, a translational repressor4 that blocks V-ATPase synthesis. Activated lysosomes, in turn, promote a metabolic shift that mobilizes protein aggregates for degradation, and reset proteostasis by enveloping and clearing the aggregates. Lysosome acidification also occurs during Xenopus oocyte maturation; thus, a lysosomal switch that enhances oocyte proteostasis in anticipation of fertilization may be conserved in other species.

A New Day in Cancer Treatment

Originally posted by Jack Hidary on his LinkedIn account:

[Excerpt] …

3/ A third approach that has yet to reach the clinic, but will in the next 5 years is nanomedicine. There are a number of funded companies working on nanomedical devices such as one which can sop up a decoy chemical produced by tumors to hide from the body’s immune system. These are not pharmacological agents, but instead act in a machine-like manner to help the body fight cancer.

Image Source: nano.cancer.gov

Full post here

Le Chatelier’s Principle on the Nanoscale

Abstract Image

Photothermal desorption of molecules from plasmonic nanoparticles is an example of a light-triggered molecular release due to heating of the system. However, this phenomenon ought to work only if the molecule–nanoparticle interaction is exothermic in nature. In this study, we compare protein adsorption behavior onto gold nanoparticles for both endothermic and exothermic complexation reactions, and demonstrate that Le Chatelier’s principle can be applied to predict protein adsorption or desorption on nanomaterial surfaces. Polyelectrolyte-wrapped gold nanorods were used as adsorption platforms for two different proteins, which we were able to adsorb/desorb from the nanorod surface depending on the thermodynamics of their interactions. Furthermore, we show that the behaviors hold up under more complex biological environments such as fetal bovine serum.

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Online game challenges players to design on/off switch for CRISPR

A team of researchers at the Stanford University School of Medicine has launched a new challenge for the online computer game Eterna in which players are being asked to design an RNA molecule capable of acting as an on/off switch for the gene-editing tool CRISPR/Cas9.

Molecular biologists will then build and test the actual molecules, based on the most promising designs provided by the players.

A gene editor as powerful as CRISPR could have unexpected effects inside living cells, so it makes sense to turn it off when it’s not needed. In addition, an on/off switch might be able to put CRISPR-influenced genes on a sort of timer, activating and deactivating them on a schedule that could mimic the way we schedule taking doses of drugs.

Faking cellular suicide (The Economist) & MIT RNA News

Faking cellular suicide could help control inflammation

And that could help treat everything from hay fever to arthritis

AS PARACELSUS first pointed out in the 16th century, it is the dose that makes the poison. Inflammation, in particular, is vital to fighting infection or healing wounds. If it lingers, however, it can cause more harm than good. Chronic inflammation often impedes the very healing that it is meant to promote. Many drugs have been invented to combat that problem, but none is as effective as doctors would like. Now, as they describe in a paper in ACS Macro Letters, a team led by Mitsuhiro Ebara at the National Institute for Materials Science in Japan have come up with a new approach. They have worked out how to persuade cells in inflamed tissues to believe that other cells nearby have just committed suicide. REST

Bio-inspired approach to RNA delivery

New technique could make it easier to use mRNA to treat disease or deliver vaccines.

By delivering strands of genetic material known as messenger RNA (mRNA) into cells, researchers can induce the cells to produce any protein encoded by the mRNA. This technique holds great potential for administering vaccines or treating diseases such as cancer, but achieving efficient delivery of mRNA has proven challenging.

Now, a team of MIT chemical engineers, inspired by the way that cells translate their own mRNA into proteins, has designed a synthetic delivery system that is four times more effective than delivering mRNA on its own. REST