Tag: biotech

Photosynthesis

Quantum coherence allows photosynthesis to operate at nearly 100% efficiency. If this effect could be used for photovoltaics.
2009-07-15: Converting the photosynthesis of rice from the less-efficient C3 form to the C4 form would increase yields by 50% and would also use water 2x as efficiently.
2014-01-09: Rubisco. This little molecule underwrites your lavish lifestyle. It isn’t a very prolific sugar daddy:

Typical enzymes can process 1000 molecules per second, but rubisco fixes only 3 CO2 molecules per second.

2015-03-28: 2x photosynthesis?

“We have unprecedented computational resources that allow us to model every stage of photosynthesis and determine where the bottlenecks are, and advances in genetic engineering will help us augment or circumvent those steps that impede efficiency. Long suggested several strategies.

Add pigments. “Our lab and others have put a gene from cyanobacteria into crop plants and found that it boosts the photosynthetic rate by 30%. Some bacteria and algae contain pigments that utilize more of the solar spectrum than plant pigments do. If added to plants, those pigments could bolster the plants’ access to solar energy.

Add the blue-green algae system. Some scientists are trying to engineer C4 photosynthesis in C3 plants, but this means altering plant anatomy, changing the expression of many genes and inserting new genes from C4 plants.

“Another, possibly simpler approach is to add to the C3 chloroplast the system used by blue-green algae”. This would increase the activity of Rubisco, an enzyme that catalyzes a vital step of the conversion of atmospheric CO2 into plant biomass. Computer models suggest adding this system would increase photosynthesis as much as 60%.

More sunlight for lower leaves. Computer analyses of the way plant leaves intercept sunlight have revealed other ways to improve photosynthesis. Many plants intercept too much light in their topmost leaves and too little in lower leaves; this probably allows them to outcompete their neighbors, but in a farmer’s field such competition is counterproductive. Studies aim to make plants’ upper leaves lighter, allowing more sunlight to penetrate to the light-starved lower leaves.

Eliminate traffic jams. “The computer model predicts that by altering this system by up-regulating some genes and down-regulating others, a 60% improvement could be achieved without any additional resource”.

In silico simulation. “The next step is to create an in silico plant to virtually simulate the amazingly complex interactions among biological scales. This type of model is essential to fill current gaps in knowledge and better direct our engineering efforts.”

2015-03-31: Improving photosynthetic efficiency from the current 1-2% would be very profound.

worldwide agricultural yields must increase by 50% by 2050. And that ambitious goal does not factor in the effects of climate change. RIPE researchers demonstrated for the first time that it was possible to improve crop yields in the field by engineering photosynthesis. By increasing the expression levels of 3 genes involved in processing light, they improved tobacco yields by 20%

2015-05-03: Artificial photosynthesis

a nanowire array captures light, and bacteria convert CO2 into acetate. The bacteria directly interact with light-absorbing materials, the first example of “microbial photoelectrosynthesis.” Another kind of bacteria then transforms the acetate into chemical precursors that can be used to make a wide range of everyday products from antibiotics to paints, replacing fossil fuels and electrical power

2016-06-05: Bionic leaf

the work addresses 2 fundamental goals: storing the energy of the sun, and building something useful from CO2 in the atmosphere, thereby reducing a major greenhouse gas.

For the new bionic leaf, Nocera’s team has designed a system in which bacteria use hydrogen from the water split by the artificial leaf plus CO2 from the atmosphere to make a bioplastic that the bacteria store inside themselves as fuel. “I can then put the bug [bacteria] in the soil because it has already used the sunlight to make the bioplastic. Then the bug pulls nitrogen from the air and uses the bioplastic, which is basically stored hydrogen, to drive the fixation cycle to make ammonia for fertilizing crops.” The researchers have used their approach to grow 5 crop cycles of radishes. The vegetables receiving the bionic-leaf-derived fertilizer weigh 150% more than the control crops. The next step is to boost throughput so that 1 day, farmers in India or sub-Saharan Africa can produce their own fertilizer with this method.

there’s also

Researchers have engineered a potentially game-changing solar cell that cheaply and efficiently converts atmospheric CO2 directly into usable hydrocarbon fuel, using only sunlight for energy.

2019-01-11: More on improving RuBisCO:

Unfortunately, RuBisCO is, well, terrible at its job. It might not be obvious based on the plant growth around us, but the enzyme is not especially efficient at catalyzing the CO2 reaction. And, worse still, it often uses oxygen instead. This produces a useless byproduct that, if allowed to build up, will eventually shut down photosynthesis entirely. It’s estimated that crops such as wheat and rice lose anywhere from 20-50% of their growth potential due to this byproduct. While plants have evolved ways of dealing with this byproduct, they’re not especially efficient. So a group of researchers at the University of Illinois, Urbana decided to step in and engineer a better way. The result? In field tests, the engineered plants grew up to 40% more mass than ones that relied on the normal pathways.

2020-08-10: Plants are Green to reduce Photosynthesis Noise. Plants ignore the most energy-rich part of sunlight because stability matters more than efficiency
2022-07-04: Acetate could be a photosynthesis alternative

Experiments showed that a wide range of food-producing organisms can be grown in the dark directly on the acetate-rich electrolyzer output, including green algae, yeast, and fungal mycelium that produce mushrooms. Producing algae with this technology is 4x more energy efficient than growing it photosynthetically. Yeast production is 18x more energy efficient than how it is typically cultivated using sugar extracted from corn. “We found that a wide range of crops could take the acetate we provided and build it into the major molecular building blocks an organism needs to grow and thrive. With some breeding and engineering that we are currently working on we might be able to grow crops with acetate as an extra energy source to boost crop yields.”

2022-08-22: Better gene regulation increases yield by 20%

“Plants dissipate potentially damaging excess absorbed light energy in full sunlight by inducing a mechanism termed nonphotochemical quenching (NPQ),” the investigators explained. However, when the leaves are shaded (by other leaves, clouds, or the sun moving in the sky) this photoprotection needs to switch off so the leaves can continue the photosynthesis process with a reserve of sunlight.

It takes several minutes for the plant to switch off the protective mechanism, costing plants valuable time that could have been used for photosynthesis. “… NPQ mechanisms are slow to relax following the frequent sun–shade transitions that occur within crop canopies”. This results in 7.5% to 30% loss of photochemical energy that could otherwise be used for photosynthesis. “For soybean crop canopies, this slow NPQ relaxation upon sun–shade transitions was calculated to cost >11% of daily CO2 assimilation”. Modifications resulted in a 20% increase in yield, and importantly, without impacting seed quality. “Despite higher yield, seed protein content was unchanged. This suggests some of the extra energy gained from improved photosynthesis was likely diverted to the nitrogen-fixing bacteria in the plant’s nodules.”

Mammoth deextinction

by inserting this modified DNA into an elephant’s egg cell, and implanting it in an elephant’s womb, you could create a modified elephant that’s nearly identical to the original mammoth

The far north could probably handle the mammoth deextinction.

2021-09-29: Colossal

The company, named Colossal, aims to place 1000s of these magnificent beasts back on the Siberian tundra, 1000s of years after they went extinct. “This is a major milestone for us,” said George Church, a biologist at Harvard Medical School, who for 8 years has been leading a small team of moonlighting researchers developing the tools for reviving mammoths. “It’s going to make all the difference in the world.” Today the tundra is dominated by moss. But when woolly mammoths were around, it was largely grassland. Some researchers have argued that woolly mammoths were ecosystem engineers, maintaining the grasslands by breaking up moss, knocking down trees and providing fertilizer with their droppings. Russian ecologists have imported bison and other living species to a preserve in Siberia they’ve dubbed Pleistocene Park, in the hopes of turning the tundra back to grassland. Dr. Church argued that resurrected woolly mammoths would be able to do this more efficiently. The restored grassland would keep the soil from melting and eroding, he argued, and might even lock away heat-trapping CO2. Initially, Dr. Church envisioned implanting embryos into surrogate female elephants. But he eventually soured on the idea. Even if he could figure out in vitro fertilization for elephants — which no one has done before — building a herd would be impractical, since he would need so many surrogates. Instead, Dr. Church decided to make an artificial mammoth uterus lined with uterine tissue grown from stem cells. “I’m not making a bold prediction this is going to be easy, but everything up to this point has been relatively easy. Every tissue we’ve gone after, we’ve been able to get a recipe for.”

Antibiotics

For all you antibacterial soap-using dummies.

Unlike (soap and other) traditional cleaners, antibacterial products leave surface residues, creating conditions that may foster the development of resistant bacteria. Alcohol-based hand sanitizers are just about as effective against germs as soap and water. They’re also easier on your skin than hand-washing, and unlike antibacterial soaps, they don’t breed antibiotic-resistant superbacteria.

The bottom line is that you shouldn’t live in fear of high-traffic surfaces. This type of contact simply isn’t the way people get sick.

2010-11-08: We are essentially back to an era with no antibiotics

This new resistance pattern has been reported in many different types of bacteria compared to previously and 10% of these NDM1-containing strains appears to be pan-resistant, which means that there is no known antibiotic that can treat it. A second concern is that there is no significant new drug development for antimicrobials.

2015-01-08: New Antibiotics Platform?

A lot of people have had similar ideas to this one, based on the fact that the overwhelming majority of bacteria in any given environmental sample can’t be readily cultured. These organisms may well be able to produce useful antibiotics and other natural products, but how will you ever be able to tell if you can’t fish any of them out? Using this on a soil sample from Maine and leaving the chip in situ for a month, a number of colonies formed. These were tested for their ability to grow outside the device in fermentation broth, and extracts of these were tested against pre-grown lawns of an S. aureus strain to look for useful antibiotic activity. Lo and behold, one extract cleared out a large spot – it turned out to come from a newly described bacterium (Eleftheria terrae, provisionally). The compound present has been named teixobactin, and here it is. So how useful is the compound? It’s active only against gram-positive organisms, which is too bad, because we could really use some new gram-negative killers (their cell membranes make them a tougher breed). But the mechanism of action turns out to be interesting: studies of S. aureus with labeled precursors showed that teixobactin is a peptidoglycan synthesis inhibitor, but extended exposure and passaging did not yield any resistant strains. That’s close to impossible if an antibiotic is binding a particular protein target – stepping on the selection pressure will usually turn up something that evades the drug. When you don’t see that, it’s often because there’s some nonspecific non-protein-targeted mechanism, which can be problematic, but teixobactin isn’t toxic to eukaryotic cells in culture (and has a favorable tox profile in mice as well). It turns out that it binds to some of the peptidoglycan precursors, lipid II and lipid III. Vancomycin has a similar mechanism (binding to lipid II), but teixobactin has a wider spectrum of activity against lipid II variants (and lipid III as well). This mechanism makes developing resistance not so straightforward – the selection pressure is more of a bounce shot than a direct hit.

2015-02-24: Antibiotics market failure

we seem willing to pay $100K or more for cancer drugs that cure no one and at best add weeks or a few months to life. We are willing to pay 1$0Ks for knee surgery that, at best, improves function but is not lifesaving. So why won’t we pay $10K for a lifesaving antibiotic?

2015-03-31: Medieval salve kills MRSA. Impressive! Not all ancient medical knowledge is homeopathic nonsense.

Take cropleek and garlic, of both equal quantities, pound them well together… take wine and bullocks gall, mix with the leek… let it stand 9 days in the brass vessel

So goes a 1000-year-old Anglo Saxon recipe to vanquish a stye, an infected eyelash follicle. If the 9th Century recipe does lead to new drugs, they might be useful against MRSA skin infections such as those that cause foot ulcers in people with diabetes. These are usually antibiotic-resistant

2016-01-23: Antibiotics synthesis

Antibiotics are generally synthesized in nature by bacteria (or other microbes) as defenses against each other. We have identified antibiotics in the lab, and thus necessarily only those made by bacterial species that we can grow in the lab. Almost all bacterial species cannot be grown in the lab using practical methods. That hasn’t changed for decades. But those bacteria grow fine in the environment, typically the soil. So… can we isolate antibiotics from the soil?

2018-05-21: Phage Therapy

3 months earlier, Patterson had suddenly fallen ill, so severely that he had to be medevaced to Germany and then to UCSD. There were several things wrong—a gallstone, an abscess in his pancreas—but the core of the problem was an infection with a superbug, a bacterium named Acinetobacter baumannii that was resistant to every antibiotic his medical team tried to treat it with. Patterson was wasted, his cheekbones jutting through his skin. Intravenous lines snaked into his arms and neck, and tubes to carry away seepage pierced his abdomen. He was delirious and his blood pressure was falling, and the medical staff had sedated him and intubated him to make sure he got the oxygen he needed. He was dying. … “We are running out of options to save Tom. What do you think about phage therapy?”

2019-11-04: CRISPR Antibiotics

An alarming number of bacteria are now resistant to one or more antibiotics, so this new line of inquiry would certainly be welcomed if it proves effective.

In their recent study, Dr. Edgell and his colleagues successfully used a Crispr-associated enzyme called Cas9 to eliminate a species of Salmonella. By programming the Cas9 to view the bacterium itself as the enemy, Dr. Edgell and his colleagues were able to force Salmonella to make lethal cuts to its own genome.

As we discover more of the benefits of our microbiota, it would also be interesting to have a solution to bacterial infections which doesn’t create problems for our “good bacteria.

2020-02-22: Antibiotics ML

So overall, this is an impressive paper. The combination of what appears to be pretty rigorous ML work with actual assay data generated just for this project seems to have worked out well, and represents, I would say, the current state of the art. It is not the “Here’s your drug!” virtual screening of fond hopes and press releases, but it’s a real improvement on what’s come before and seems to have generated things that are well worth following up on. I would be very interested indeed in seeing such technology applied to other drug targets and other data sets – but then, that’s what people all around academia and industry are trying to do right now. Let’s hope that they’re doing it with the scope and the attention to detail presented in this work.

2020-07-24: SCH-79797

Researchers have found a compound, SCH-79797, that can simultaneously puncture bacterial walls and destroy folate within their cells — while being immune to antibiotic resistance. This is the first antibiotic that can target Gram-positives and Gram-negatives without resistance

2020-08-07: Maybe the non-profit route will work

If something isn’t done now, antibiotic-resistant bacteria could kill as many as 10M people a year by 2050. A little-known Boston nonprofit could be our best hope.

2021-07-28: Biofilms are nasty

This discovery underscores how important it is to include biofilms in any studies of antibacterial compounds because being able to kill planktonic cultures bears no relation to being able to break down biofilm.

2021-10-14: Another approach is to modify bacteria to destroy the MSRA biofilms

Bacteria present a promising delivery system for treating human diseases. Here, we engineered the genome-reduced human lung pathogen Mycoplasma pneumoniae as a live biotherapeutic to treat biofilm-associated bacterial infections. This strain has a unique genetic code, which hinders gene transfer to most other bacterial genera, and it lacks a cell wall, which allows it to express proteins that target peptidoglycans of pathogenic bacteria. We first determined that removal of the pathogenic factors fully attenuated the chassis strain in vivo. We then designed synthetic promoters and identified an endogenous peptide signal sequence that, when fused to heterologous proteins, promotes efficient secretion. Based on this, we equipped the chassis strain with a genetic platform designed to secrete antibiofilm and bactericidal enzymes, resulting in a strain capable of dissolving Staphylococcus aureus biofilms preformed on catheters in vitro, ex vivo, and in vivo. To our knowledge, this is the first engineered genome-reduced bacterium that can fight against clinically relevant biofilm-associated bacterial infections.

2023-05-23: Odd that phage therapy only made progress in former soviet republics

“Phages” are little known outside the former countries of the Soviet Union, which did the most to develop the idea. In Georgia they have been part of the local pharmacopoeia for decades. (Indeed, 2023 marks the Eliava’s centenary.) Little vials containing stale-tasting liquid full of anti-bacterial viruses can be bought at pharmacies across Tbilisi. Now, as worries about antibiotic resistance build, Western firms are taking a second look.

Microbiome

Human microbiome program?

Because of the importance of beneficial / commensal microbes in human biology, there have been growing efforts to characterize the microbes in various body locations – gut, mouth, lungs, skin, etc. But the efforts so far have simply given a tantalizing taste of how interesting and important these microbes are. So here comes this meeting. Organized by NIH (specifically, Francis Collins at NHGRI), this workshop is geared to discuss the possibility that studies of the human microbiome will be included in the next list of “NIH Roadmap” programs. More on the NIH Roadmap some other time.

Basically, the general idea is – do we need an big scale, organized program to tackle the human microbiome.? To get us in the mood, we had talks by many of the pioneers/leaders in the field (e.g., David Relman, Jeff Gordon, Jim Tiedje) as well as discussion of the NIH Roadmap program. I personally did not need any convincing but it was good to hear some of the ideas presented. In the end, I think there is no doubt that a large scale Human Microbiome Program is needed and would be very beneficial.

In addition to the 10 trillion human cells, there are 100 trillion bacterial cells in a body. Our metagenome may be 100x the human genome.
2010-10-30: Space Standard Microbiome. Venter suggests NASA should replace the microbiome (bacteria species) of astronauts with a standardized, synthetic one to improve survivability of space flight.
2012-06-15: 0.3% Human

Where the human genome carries some 22K protein-coding genes, the human microbiome contributes some 8M protein-coding genes responsible for human survival: 360x more.

The microbiome is one of the most fascinating areas in biology:

in many mammals a microbial community ferments various sweats, oozes and excretions into distinctive scents that reveal age, health and much more to knowing noses in a select social circle.

That’s right, microbes are posting status updates to each other through smells, sharing with other microbes what they’ve learned about host animals.
2012-12-08: American Gut looks amazing. I will of course participate. Since you are only 10% human (the rest is bacteria), even if you do 23andme you don’t really know yourself at all. $99 for 1 bacterial DNA kit, $180 for 2. There are also higher levels, up to the $25k ultra-deep sequencing of your microbiome sample aimed at generating as many individual bacterial genomes as possible.
2015-03-03: a nice summary of The American Gut project

2016-10-01: Poop Bot. As usual, onion’s satire is leading the way:

you can tell the most about someone by sampling their microbiome, and “the sewage system is the great aggregator.” Gross, sure, but Ratti is studying waste to understand everything from heroin use to antibiotic-resistant bacteria—and all with the help of a sewer-slurping robot named Luigi.

2017-09-05: Microbiome 99% unknown

A survey of DNA fragments circulating in the blood suggests the microbes living within us are vastly more diverse than previously known. In fact, 99% of that DNA has never been seen before. The “vast majority” of it belonged to a phylum called proteobacteria, which includes, among many other species, pathogens such as E. coli and Salmonella. Previously unidentified viruses in the torque teno family, generally not associated with disease but often found in immunocompromised patients, made up the largest group of viruses.

2018-10-03: SynBioBeta 2018

In 15 years, brain interfaces will be as common as the cell phone. The radical experiment that has been run over the past 100 years shifting the microbiome of infants and provoking a wide array of immune disorders (allergies, asthma, diabetes)

2019-08-07: Microbiome Friendships?

Now that it is clear that social behavior plays a role in shaping the gut microbiome, the next question is whether microbiomes have had a meaningful impact on our social worlds. Scientists still do not have an answer, but they are tantalized by the possibilities, which could have implications for understanding the evolution of sociality.

2019-12-04: Microbiomes Affect Fear

microbiomes can influence the fear responses of their hosts, possibly by releasing compounds that affect the brain’s neuroanatomy and function.

2022-02-22: Space microbiome

Humans aren’t the only organisms that we have to consider when evaluating the impacts of space travel. While we are traveling on spaceships, microbes are traveling on us. Microgravity has been shown to alter bacterial growth patterns and kinetics, and radiation increases the frequency of mutations—in both cases creating opportunities for increased antimicrobial resistance—all in an environment where astronauts immune systems are compromised. The ISS has a complex microbiome that we fundamentally alter, and that in turn alters us. It’s important to be able to understand the genetic basis of antimicrobial resistance in space. A team of researchers carried out a study with the goal of addressing this question. A considerable number of AMR genes were found in several different locations for Kalamiella piersonii—a microbe potentially involved in causing urinary tract infections. Worryingly, “the potentially very pathogenic microbe E. bugandensis was found in location 2 (forward side panel wall of the Waste and Hygiene Compartment) in flight 1, presenting more than 40 ARGs.” They were also able to detect specific types of potential drug resistance for several microbes within the Pantoea species—which provided a higher level of resolution into observations made in their past analysis.

2023-01-19: person-to-person transmission

Mother-to-infant gut microbiome transmission was considerable and stable during infancy (around 50% of the same strains among shared species (strain-sharing rate)) and remained detectable at older ages. By contrast, the transmission of the oral microbiome occurred largely horizontally and was enhanced by the duration of cohabitation. There was substantial strain sharing among cohabiting individuals, with 12% and 32% median strain-sharing rates for the gut and oral microbiomes, and time since cohabitation affected strain sharing more than age or genetics did.

2023-05-04: Using dental plaque to reconstruct the oral microbiome

Reconstructing an oral microbiome—a soup of 100s of different bacterial species, and millions of individual bacteria—from degraded ancient DNA is “like throwing together pieces of many puzzles and trying to solve them with the pieces mixed up and some pieces missing entirely”.

It took 3 years to adapt DNA sequencing tools and computer programs to work with the much shorter fragments of DNA found in ancient samples. Drawing on dental calculus from 46 ancient skeletons—including a dozen Neanderthals and modern humans who died between 30k and 150 years ago, Warinner identified DNA from 10s of extinct or previously unknown oral bacteria.
Identified as a type of bacterium called a chlorobium, its modern relatives use photosynthesis to survive on small amounts of light and live in anaerobic conditions, such as stagnant water. They aren’t found in modern mouths and appear to have vanished from ancient humans 10 ka BP. This chlorobium might have entered the mouths of ancient people because they drank water in or near caves. Or it might once have been a normal part of some people’s ancient oral microbiome, surviving on faint light penetrating the cheek.

2023-06-08: Sample handling ruins many studies

The authors have tried all sorts of sample-handling variations, and it looks like they have had trouble finding any that don’t change the composition of the microbial samples themselves. Both papers investigated the 2 commercially available stool sample kits (OMNIgene and Zymo), and found that the latter was much more sensitive to temperature variations on storage. And both kits changed the absolute levels of various bacteria types: the OMNIgene-preserved samples had significantly higher amounts of Bacteroidetes species as compared to preservative-free controls, while the Zymo-preserved ones had significantly lower amounts. The second paper also finds that the method used for cell disruption can significantly affect the ribosomal RNA reads used to characterize the bacterial species as well.

Researchers in the field should also be measuring total bacterial load in their samples and monitoring that for signs of variability in their sample handling and people should standardize on 25 PCR cycles, because that can also change things. These effects can help explain the widely varying literature results in human microbiome studies.