Daily Archives: September 17, 2023

Illustration of a colon cancer cell. [Image: Kateryna Kon / Science Photo Library / Getty Images]

The treatment of malignant tumors has long presented a challenge for cancer researchers. Bacteria-based therapiesin which microbes, often souped-up by genetic engineering or nanotechnology, are put to work as on-site cancer killersshow promise for improving upon conventional methods. But these techniques have drawbacks, including the risk of antibiotic resistanceand the need for complicated procedures that could degrade the bacteria.

Now, researchers in Japan have demonstrated a new approach for enhancing purple photosynthetic bacteria, which they say is an ideal strain for effective cancer phototherapy (Nano Today, doi: 10.1016/j.nantod.2023.101966). Their process, which involves simple chemical functionalization, preserves the innate medicinal qualities of the bacteria while enhancing their ability to fight cancer.

The researchers chose the purple photosynthetic bacteria Rhodopseudomonas palustris(RP) as an optimal candidate for cancer treatment because it is spatiotemporally activatable by near-infrared light and shows strong photothermal conversionthe ability to turn laser light energy into heat, in this case to selectively eliminate cancer cells. This is thanks to its bacteriochlorophyll (BChl) light-harvesting nanocomplexes, which are useful for targeted optical cancer therapies.

RP demonstrated excellent properties, such as near-infrared (NIR) fluorescence, photothermal conversion and low cytotoxicity, explainedlead author Eijiro Miyako, Japan Advanced Institute of Science and Technology (JAIST), in a press release accompanying the paper.Itabsorbs NIR light and produces free radicalsa property that can be utilized to kill cancer cells.

The membranes of photosynthetic bacteria were PEGylated, and fluorescent markers and an anti-PD-L1 antibody were attached to enable tumor-targeting and immunological activation. The engineered bacteria demonstrated effective tumor suppression and immunological responses in a mouse model of colon cancer. [Image: Eijiro Miyako] [Enlarge image]

After selecting their preferred bacteria, the researchers looked to improve them through a series of modifications. First, they attached polyethylene glycol (PEG) derivatives, including one called Biocompatible Anchor for Membrane (BAM), to the bacterial cell walls. Known as PEGylation, this process has a number of benefits, including helping the complex evade host immune response and facilitating attachment of other biomolecules. The team then affixed a fluorescent Alexa488-BSA conjugate to the BAM, which allowed it to be tracked with fluorescence microscopy and used for locating tumors.

Finally, the researchers tacked on an immune checkpoint inhibitor antibody known as anti-PD-L1 using the same BAM method. Cancer cells express a protein called Programmed Cell Death Ligand 1 (PD-L1), which suppresses the hosts immune response and allows cancer cells to evade detection and elimination. Anti-PD-L1 antibodies block PD-L1, thus preventing cancer cells from flying under the immune radar and allowing them to be targeted by the hosts immune system.

To examine the efficacy of the various bacterial complexes, the researchers pitted them against colon cancer in mice in a series of experiments. Tests showed that anti-PD-L1BAMRP, BAMRP and RP inhibited tumor growth when injected in mice with colon cancer. However, all the varieties had an especially dramatic anticancer effect when excited with an NIR laser at 0.7 W for 3 minutes.

During the 30-day follow-up period after the experiment, solid tumors disappeared completely in mice that underwent laser irradiation of injected anti-PD-L1BAMRP, BAMRP, or RP. Laser-induced anti-PD-L1BAMRP was the most effective during the primary treatment stage and also cured tumors faster than the others.

Our findingsrevealed that light-driven functional bacteria demonstrated effective optical and immunological functions in the murine model of colon cancer. Moreover, the NIR fluorescence of the engineered bacterial complexes was used to locate tumors, effectively paving the way for future clinical translation, saysMiyako. We believe that this bacterial technology could be available for clinical trials in 10 years and have positive implications for cancer diagnosis and therapy.

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Targeting Tumors with Photosynthetic Bacteria - Optics & Photonics News

Researchers have utilized in-cell engineering to produce hybrid solid catalysts for artificial photosynthesis using protein crystals. These catalysts, created through genetically modified bacteria, are highly active, durable, and eco-friendly, paving the way for a novel approach in enzyme immobilization.

Researchers at Tokyo Tech have demonstrated that in-cell engineering is an effective method for creating functional protein crystals with promising catalytic properties. By harnessing genetically altered bacteria as a green synthesis platform, the researchers produced hybrid solid catalysts for artificial photosynthesis. These catalysts exhibit high activity, stability, and durability, highlighting the potential of the proposed innovative approach.

Protein crystals, like regular crystals, are well-ordered molecular structures with diverse properties and a huge potential for customization. They can assemble naturally from materials found within cells, which not only greatly reduces the synthesis costs but also lessens their environmental impact.

Although protein crystals are promising as catalysts because they can host various functional molecules, current techniques only enable the attachment of small molecules and simple proteins. Thus, it is imperative to find ways to produce protein crystals bearing both natural enzymes and synthetic functional molecules to tap their full potential for enzyme immobilization.

Against this backdrop, a team of researchers from Tokyo Institute of Technology (Tokyo Tech) led by Professor Takafumi Ueno has developed an innovative strategy to produce hybrid solid catalysts based on protein crystals. As explained in their paperpublished inNano Letterson 12 July 2023, their approach combines in-cell engineering and a simplein vitroprocess to produce catalysts for artificial photosynthesis.

Graphic explaining the research. Credit: Professor Takafumi Ueno, Tokyo Institute of Technology

The building block of the hybrid catalyst is a protein monomer derived from a virus that infects theBombyx morisilkworm. The researchers introduced the gene that codes for this protein intoEscherichia colibacteria, where the produced monomers formed trimers that, in turn, spontaneously assembled into stable polyhedra crystals (PhCs) by binding to each other through their N-terminal -helix (H1). Additionally, the researchers introduced a modified version of the formate dehydrogenase (FDH) gene from a species of yeast into theE. coligenome. This gene caused the bacteria to produce FDH enzymes with H1 terminals, leading to the formation of hybrid H1-FDH@PhC crystals within the cells.

The team extracted the hybrid crystals out of theE. coli bacteria through sonication and gradient centrifugation and soaked them in a solution containing an artificial photosensitizer called eosin Y (EY). As a result, the protein monomers, which had been genetically modified such that their central channel could host an eosin Y molecule, facilitated the stable binding of EY to the hybrid crystal in large quantities.

Through this ingenious process, the team managed to produce highly active, recyclable, and thermally stable EYH1-FDH@PhC catalysts that can convert carbon dioxide (CO2) into formate (HCOO) upon exposure to light, mimicking photosynthesis. In addition, they maintained 94.4% of their catalytic activity after immobilization compared to that of the free enzyme. The conversion efficiency of the proposed hybrid crystal was an order of magnitude higher than that of previously reported compounds for enzymatic artificial photosynthesis based on FDH, highlights Prof. Ueno. Moreover, the hybrid PhC remained in the solid protein assembly state after enduring bothin vivoandin vitroengineering processes, demonstrating the remarkable crystallizing capacity and strong plasticity of PhCs as encapsulating scaffolds.

Overall, this study showcases the potential of bioengineering in facilitating the synthesis of complex functional materials. The combination ofin vivoandin vitrotechniques for the encapsulation of protein crystals will likely provide an effective and environmentally friendly strategy for research in the areas of nanomaterials and artificial photosynthesis, concludes Prof. Ueno.

And we sure hope that these efforts will lead us to a greener future!

Reference: In-Cell Engineering of Protein Crystals into Hybrid Solid Catalysts for Artificial Photosynthesis by Tiezheng Pan, Basudev Maity, Satoshi Abe, Taiki Morita and Takafumi Ueno, 12 July 2023, Nano Letters. DOI: 10.1021/acs.nanolett.3c02355

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Artificial Photosynthesis Breakthrough Researchers Produce ... - SciTechDaily

The European Patent Office (EPO) has rejected an opposition filed against a BASF (Nunhems) patent on watermelons with bushy growth habit (EP2814316). No Patents on Seeds! filed the opposition because the patent is not inventive and patents on conventionally-bred plant varieties are prohibited.

The bushy growth of the plants was a random occurrence and, according to the patent description, the plants were simply a discovery in a home-garden. Their advantage: less land is needed for cultivation. The EPO granted the patent in 2021 as the patent holder had applied an additional well-established method (for generating triploid plants) to reduce the number of kernels. Clearly, neither the applied method nor the detection of the bushy growth habit is based on an invention.

Christoph Then, coordinator at No Patents on Seeds! the international coalition that filed the opposition: The EPO decision is in direct contradiction to the law and to the basic principles of the patent system. No one can claim an invention if a discovery is combined with well-known methods and the results are not surprising. The prohibitions in regard to patentability of conventional bred plants are severely violated. This decision is setting an extreme precedence in regard to life patents.

Patents can only be granted if the plant characteristics are obtained from genetic engineering

According to European patent law, patents on plant varieties are generally prohibited. Patents can only be granted if the plant characteristics are obtained from genetic engineering.

In Europe, the plant variety protection (PVP) law guarantees that breeders can use all conventionally-bred varieties to breed and market improved varieties. In contrast, patents can be used to hamper or block access to biodiversity needed by all breeders. If such patents are granted, only big companies can survive in the long-term, and they will then decide what is grown and harvested, as well as what food is marketed at which price.

No Patents on Seeds! plans to appeal the EPO decision and is demanding that politicians take their responsibility seriously and finally implement the existing prohibitions in patent law. Patents on conventionally-bred plants and animals have to be stopped. The Austrian government has already decided to amend national patent laws as a first step, other European countries may follow soon.

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BASF patent on watermelons upheld: European Patent Office rejects ... - Bio Eco Actual

Analysts are concerned that a lack of skilled labor in the space industry "could impact aerospace's growth in recent years, putting key projects on hold or preventing space startups from gaining traction," reports ExtremeTech. From the report: According to the Space Foundation's annual Space Report, job opportunities within the U.S. space industry have grown 18% over the past five years. Meanwhile, American colleges saw a decline in engineering students across the same period, prompting the industry to wonder whether the workforce could keep up with demand. Indeed, the Space Foundation says only 17% of NASA's workforce is under 35; not only does the agency tend to hire workers who have accumulated a lot of experience, but there aren't as many young professionals under consideration as there could be.

The industry isn't just short on engineers, though. Although STEM degrees requiring an intimate familiarity with astronomy, physics, robotics, computing, mathematics, and other technical topics are certainly one path toward space, the industry relies on workers proficient in a much wider range of skills. Welders, electricians, crane operators, and other blue-collar workers are essential to manufacturing and ground operations. In contrast, marketers, PR representatives, bookkeepers, lawyers, and other office workers keep things running in the background. In fact, as of writing, SpaceX is even hiring a barista.

As Space Foundation CEO Tom Zelibor put it in the nonprofit's Q1 2023 report, the space industry might benefit from informing the public of the benefits of space exploration. These benefits are apparent to some, but others find space exploration nonessential or frivolous. Other people interested in the space industry might be scared off from pursuing it as a career, thanks to its reputation for requiring advanced degrees and mathematical prowess. From the Space Foundation's own educational projects to those run by The Planetary Society and Space for Humanity, public outreach could be the key to bolstering industry engagement. The report notes that the "space economy" has ballooned to $464 billion (up 159% from 2010) and is predicted to reach a $1 trillion valuation by 2030, according to some analysts.

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Space Industry Is Growing Faster Than Its Workforce, Analysts Say - Slashdot

This week saw an announcement from the University of Chicago's Pritzker School of Molecular Engineering. A new type of vaccine "has shown in the lab setting that it can completely reverse autoimmune diseases like multiple sclerosis and type 1 diabetes all without shutting down the rest of the immune system." A typical vaccine teaches the human immune system to recognize a virus or bacteria as an enemy that should be attacked. The new "inverse vaccine" does just the opposite: it removes the immune system's memory of one molecule. While such immune memory erasure would be unwanted for infectious diseases, it can stop autoimmune reactions like those seen in multiple sclerosis, type I diabetes, or rheumatoid arthritis, in which the immune system attacks a person's healthy tissues. The inverse vaccine, described in Nature Biomedical Engineering, takes advantage of how the liver naturally marks molecules from broken-down cells with "do not attack" flags to prevent autoimmune reactions to cells that die by natural processes. Pritzker School of Molecular Engineering researchers coupled an antigen a molecule being attacked by the immune system with a molecule resembling a fragment of an aged cell that the liver would recognize as friend, rather than foe. The team showed how the vaccine could successfully stop the autoimmune reaction associated with a multiple-sclerosis-like disease...

Jeffrey Hubbell [lead author of the new paper] and his colleagues knew that the body has a mechanism for ensuring that immune reactions don't occur in response to every damaged cell in the body a phenomenon known as peripheral immune tolerance, which is carried out in the liver. They discovered in recent years that tagging molecules with a sugar known as N-acetylgalactosamine (pGal) could mimic this process, sending the molecules to the liver where tolerance to them develops. "The idea is that we can attach any molecule we want to pGal and it will teach the immune system to tolerate it," explained Hubbell. "Rather than rev up immunity as with a vaccine, we can tamp it down in a very specific way with an inverse vaccine."

In the new study, the researchers focused on a multiple-sclerosis-like disease in which the immune system attacks myelin, leading to weakness and numbness, loss of vision and, eventually mobility problems and paralysis. The team linked myelin proteins to pGal and tested the effect of the new inverse vaccine. The immune system, they found, stopped attacking myelin, allowing nerves to function correctly again and reversing symptoms of disease in animals. In a series of other experiments, the scientists showed that the same approach worked to minimize other ongoing immune reactions...

Initial phase I safety trials of a glycosylation-modified antigen therapy based on this preclinical work have already been carried out in people with celiac disease, an autoimmune disease that is associated with eating wheat, barley and rye, and phase I safety trials are under way in multiple sclerosis. Those trials are conducted by the pharmaceutical company Anokion SA, which helped fund the new work and which Hubbell cofounded and is a consultant, board member, and equity holder. The Alper Family Foundation also helped fund the research.

"There are no clinically approved inverse vaccines yet, but we're incredibly excited about moving this technology forward," says Hubbell. Thanks to Slashdot reader laughingskeptic for sharing the news.

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New 'Inverse Vaccine' Shows Potential to Treat MS and Other ... - Slashdot