Category Archives: Transhuman News

Scientists led by a team at the University of Minnesota Twin Cities say they have developed a novel method that allows scientists and engineers to visualize mRNA molecules in the brains of living micereportedly for the first time. The study reveals new insights into how memories are formed and stored in the brain and could provide scientists with new information about diseases such as Alzheimers, according to the researchers who published their work Real-time visualization of mRNA synthesis during memory formation in live mice in Proceedings of the National Academy of Sciences (PNAS).

It is well known that mRNA is produced during the process of forming and storing memories, but the technology for studying this process on the cellular level has been limited. Previous studies have often involved dissecting mice in order to examine their brains. The new technique gives scientists a window into RNA synthesis in the brain of a mouse while it is still alive.

Memories are thought to be encoded in populations of neurons called memory trace or engram cells. However, little is known about the dynamics of these cells because of the difficulty in real-time monitoring of them over long periods of time invivo. To overcome this limitation, we present a genetically encoded RNA indicator (GERI) mouse for intravital chronic imaging of endogenousArcmessenger RNA (mRNA)a popular marker for memory trace cells, write the investigators.

We used our GERI to identifyArc-positive neurons in real time without the delay associated with reporter protein expression in conventional approaches. We found that theArc-positive neuronal populations rapidly turned over within 2 d in the hippocampal CA1 region, whereas 4% of neurons in the retrosplenial cortex consistently expressedArcfollowing contextual fear conditioning and repeated memory retrievals. Dual imaging of GERI and a calcium indicator in CA1 of mice navigating a virtual reality environment revealed that only the population of neurons expressingArcduring both encoding and retrieval exhibited relatively high calcium activity in a context-specific manner.

This invivo RNA-imaging approach opens the possibility of unraveling the dynamics of the neuronal population underlying various learning and memory processes.

We still know little about memories in the brain, explained Hye Yoon Park, PhD, an associate professor in the University of Minnesota department of electrical and computer engineering and the studys lead author. Its well known that mRNA synthesis is important for memory, but it was never possible to image this in a live brain. Our work is an important contribution to this field. We now have this new technology that neurobiologists can use for various different experiments and memory tests in the future.

The process involved genetic engineering, two-photon excitation microscopy, and optimized image processing software. By genetically modifying a mouse so that it produced mRNA labeled with green fluorescent proteins, the researchers were able to see when and where the mouses brain generated Arc mRNA, the specific type of molecule they were looking for.

Because the mouse is alive, the scientists could study it for longer periods of time. Using this new process, the researchers performed two experiments on the mouse in which they were able to see in real time over a month what the neurons were doing as the mouse was forming and storing memories.

Historically,neuroscientists have theorized that certain groups of neurons in the brain fire when a memory is formed, and that those same cells fire again when that moment or event is remembered.However, in both experiments, the researchers found that different groups of neurons fired each day they triggered the memory in the mouse.

Over the course of several days after the mouse created this memory, they were able to locate a small group of cells that overlapped, or consistently generated the Arc mRNA each day, in the retrosplenial cortex (RSC) region of the brain, a group which they believe is responsible for the long-term storage of that memory.

Our research is about memory generation and retrieval, Park said. If we can understand how this happens, it will be helpful for us in understanding Alzheimers disease and other memory-related diseases. Maybe people with Alzheimers disease still store the memories somewherethey just cant retrieve them. So in the very long-term, perhaps this research can help us overcome these diseases.

Scientists from Seoul National University and the Korea Institute of Science and Technology were also involved in this research.

Watch a 3D video visualizing the hippocampus region of a live mouse brain.

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Gene Expression Visualized in Brains of Live Mice in Real Time - Genetic Engineering & Biotechnology News

By Antoine Awad, chief operating officer, Synlogic, Inc.

The rise of high-throughput molecular biology and DNA sequencing, in parallel with the increased sophistication of computational models, has enabled the field of synthetic biology, where precision genetic engineering is used to program bacterial cells in much the same way we program computers to perform different functions. In 2014, our co-founders, Jim Collins and Tim Lu, recognized world experts in synthetic biology, pitched the idea to Atlas Ventures of forming the first company that would apply the principles of synthetic biology to the creation and development of biotherapeutics. The idea was that this approach would allow us to address significant medical needs using a completely new approach based on our drug candidates, which we call synthetic biotics. Within eight years, Synlogic opened five INDs with the FDA, dosed more than 350 patients, and built a clinical-stage pipeline focused on metabolic and immunological diseases. This includes achieving proof of concept in one program (in phenylketonuria, or PKU), and proof of mechanism in another (hyperoxaluria, or HOX). From the beginning, we knew that as pioneers, manufacturing would present challenges and also would be a critical success factor.

Our drug candidates to date have used the same starter strain, or chassis, a well-studied probiotic called E. coli Nissle 1917. As live potential biotherapeutics, these present unique challenges. As is the case with many biotechnology companies, especially those advancing innovative therapeutic approaches, we evaluated the benefits of outsourcing manufacturing to third parties that have specialized expertise in producing medicines based on synthetic biology. We started discussions early in our development programs and assessed all our options to determine the optimal pathway that would deliver the levels of quality and precision that are essential in development of drugs based on synthetic biology.

Using E. coli Nissle (ECN) has advantages in a history of robust safety data validated in more than 100 years of clinical research. A challenge, however, when producing ECN as synthetic biotics is the need to strike a balance between increasing cell densities and inducing target enzymes. A disproportionate focus on one of these parameters can have an adverse effect on the other. While the technology to grow cells is very effective, the cells need to be kept alive and able to maintain high viability, which is imperative to their proper function in disease targeting. Fermenting bacteria for protein production is common, but expertise in maintaining high cell viability is both essential and rare.

To help address these challenges, we reached out to contract development and manufacturing organizations (CDMOs) with specialized expertise. While many CDMOs were using fermentation techniques for industrial purposes, these technologies would not meet good manufacturing practice (GMP) standards and FDA compliance guidelines for production of biotherapeutics. Many also do not have both fermentation and lyophilization (freeze drying) capabilities under one roof. The ones that do often have limited lyophilization capacity that does not align with fermentation scaling. Among the limited number of CDMOs that will work with live bacteria, most have long lead times and high costs, especially following demands on production associated with the COVID-19 pandemic.

Given the limited options for third-party support available, Synlogic invested in manufacturing to meet our needs at every phase of development and to keep a vigilant focus on product viability. Our drugs include cells that must remain metabolically active; over time, they will die unless they are formulated into a stable powder. To minimize the duration of our processing time, we decided to co-locate fermentation and downstream processing and lyophilization to prevent cell death and maintain high drug viability. We also implemented a lyophilization step that enhances the shelf life of our therapies and allows for more patient-friendly presentation as an oral powder.

In operations involving fermenters, lyophilizers, and analytical instruments in quality control settings, automation is critical to make processes efficient and minimize production costs. For example, a fermenter for E. coli Nissle must run between 16 and 22 hours. Without automated capabilities, this process would require manufacturing operators to be on-site around the clock. Automated technologies also play a central role in helping us meet both demand and quality control (QC) requirements at every stage of the product life cycle.

Our ambr 15 and ambr 250 high-throughput automated bioreactors or fermenters are used in process development, process optimization, and scale down models. With these systems, we can test different conditions and process parameters in a short timeframe and at low volumes, which gives us a quicker path to an established process while reducing costs per experiment. We have another high-throughput automatic analyzer that enables screening and analysis of fermentation metabolites. With this production system in place, we can better understand what is required to keep cells healthy, growing, and active. The technology also allows us to be faster and more confident in our decision-making and potentially reduce cycle time.

We also implemented a range of single-use technologies throughout our facility as well as customized processes to address specific challenges in manufacturing our biotherapeutics. Single-use technology allows us to switch between programs faster by minimizing required cleaning and risk of cross-contamination. It also reduces the facility footprint, thus decreasing the necessary up-front capital investment. We also established a cleanroom that incorporates procedures and layouts that reduce the risk of microbial contamination and product cross-contamination through an air pressure cascade, segregation of product operations, and cleaning requirements.

One of the major challenges with any new technology or therapeutic approach is the ability to rapidly scale manufacturing as needed from early-stage research through to commercialization. Recognizing our needs in terms of scaling up as well as the challenges in considering both in-house capabilities and engagement of CDMOs, we quickly recognized the potential benefits of a hybrid approach.

Our physical cleanrooms come with a menu of services that can be handled by CDMOs, including inventory control, warehousing, environmental monitoring, and other support areas. Meanwhile, we built an internal infrastructure at Synlogic that is able to meet product needs based on available resources and our own highly experienced staff who are trained in GMPs. Our in-house capabilities include process development, analytical development, formulation, current GMP production, packaging and labeling, QC, and quality assurance. In a hybrid model, we have the flexibility to outsource some of the required tests and assays to labs/CROs when needed. The facility was also designed to handle our process needs with the ability to readily scale up and expand further as our development programs advance.

When planning a manufacturing strategy, it can be advantageous for biotechnology companies to co-establish research and CMC process development in the same facility, allowing for more efficient exchange of technical expertise. Generally, companies advancing a program into clinical development can often handle production needs related to Phase 1 or Phase 2 clinical trials internally when required scales are more modest.

It is important that companies consider investing in automated processes wherever feasible and recognize that scaling up can require larger equipment and potentially exponential increases in the need for raw materials and consumables, many of which can have long procurement times. Planning early is essential to address potential supply chain issues and avoid bottlenecks. It can also often be advantageous to consider collaborating with regulators and other stakeholders early in the development process. Early input from regulatory agency contacts and consultants can support smoother transitions as companies advance to later stage clinical development.

Whether companies decide to establish in-house manufacturing capabilities, outsource to CDMOs, or build a hybrid model, planning to meet production goals at every stage can require significant levels of innovation and flexibility. Teams must be prepared to address new challenges and make quick, thoughtful decisions throughout the product life cycle to be successful. These demands can be even more important in emerging areas of research such as synthetic biology that can require development of entirely new and previously untried strategies and technologies to keep manufacturing on track.

About the Author:

Antoine (Tony) Awad is chief operating officer at Synlogic. He has more than 18 years of experience in the biotech and pharma industry with substantial experience in the development and manufacturing of novel therapeutics from pre-IND studies through global commercialization. Prior to joining Synlogic, he was most recently at Abpro Therapeutics and served as senior vice president of CMC and operations, where he was responsible for the development of bi-specific antibodies for oncology and leading corporate operational functions. Previously, he was at L.E.A.F. Pharmaceuticals and Merrimack Pharmaceuticals. Awad is a graduate of Boston University and holds a bachelors degree in biochemistry and molecular biology and conducted graduate research at Boston University School of Dental Medicine.

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Manufacturing Biotherapeutics Based On Synthetic Biology Lessons Learned - BioProcess Online

Bitcoin isnt the great evil we have been led to believe. Until youve looked deeply into something, youre not in a position to judge it, says Daniel Batten.

John Lennon once said, Life is what happens when youre busy making other plans. I remembered this line today when I recalled the plans I was making for this year, and what actually happened.

For as long as I can remember, protecting the environment was my #1 value. At drama school, a friend affectionately teased me by christening me Daniel loves trees more than people Batten. In my teenage years and twenties, I was a regular on protest marches: against the confiscation of indigenous land, against Genetic Engineering, and against the logging of native forest to name a few. The most recent one I went on was 9 years ago against Deep Sea Oil Drilling off New Zealands coast.

I still remember the day a friend from Greenpeace, an organization I supported over 4 decades, rang me up to ask me to lead an action against one of McDonalds environmental practices. Together with a flock of humans dressed as chickens, we stormed the McDonalds HQ and I, dressed in Ronald McDonald-like regalia, announced my resignation. Oh, and there is a slight chance youll be arrested he mentioned at the end. I was CEO of a technology company Id founded at the time. Without telling my board what I was planning, I said yes.

Slowly it dawned on me though, I was a better supporter of technology than I was a protestor. What if I used that skill to make a difference? That led me to create a ClimateTech VC fund.

It was an easy decision. Id been investing in technology companies for 19 years, so I knew what to look for, what to avoid and how to optimize a founding teams chance of success.

We invested in companies that not only made commercial sense but who we felt proud of. One company is on a mission to decarbonize the entire Zinc industry by 2045. Another has a goal to remove 50% of all CO2 emissions from the Greenhouse industry by 2030. The way theyre going, theyll probably make it.

About the same time, a friend of mine started talking to me a lot more about Bitcoin. I felt conflicted. On one side, I could see the social good: how it helped build a world where wealth transfer from the poor to the rich via quantitative easing was no longer possible.But as an environmentalist, Id heard the stories about its energy usage and was unconvinced if it did enough good to justify its carbon emissions.

When Greenpeace came out against Bitcoin the inner conflict intensified. My Bitcoiner friend was telling me that it helped build out the renewable grid. My friends at Greenpeace were saying this was Greenwash propagated by greedy Bitcoin investors who would say anything to increase the user-adoption upon which their returns depended.

I realized I had to do my own research.

I didnt know what Id find, but I suspected the truth would lie somewhere in the middle.

For the first time in my life, I spent an extended period of time simply researching something I was curious about and wanted the answer to.

My research led me to read more about Climate Change, CO2 emissions, and methane emissions than Id ever read. Ill be honest: discovering the true enormity of the climate crisis and the task ahead of us was not easy reading. I forced myself to understand physics, energy, the jargon of the electrical grid, energy trading, and Bitcoin mining. I interviewed or listened to interviews with climate scientists, solar engineers, grid operators, analysts at utility companies, utility scale wind operators, solar installers, battery experts and onchain analysts.

Slowly but surely, a picture started to emerge from the haze. It was a consistent picture, consistently espoused by all the people I spoke to who had looked into it deeply.

The conclusion was this:

1. Bitcoin mining can be used in a way that is bad for the environment. Examples of this include the re-opening of a gas plant in NY State for the sole purpose of Bitcoin mining.

2. Bitcoin mining can also be used in a way that is good for the environment. Examples of this include the solar and wind operators I discovered who would not have got financing to build their plants had it not been for having a Bitcoin mining customer.

That looks like a neutral outcome, some arguments for and against. The outcome was anything but neutral.

I also found out

1. That the direction Bitcoin mining is heading is towards renewable energy

2. That the rate at which it is transitioning to renewable energy is faster than any other industry Id seen (as a VC who sees around 50 cleantech pitches a year, wed seen a whole stack!)

3. The current % of renewable energy use is also higher than any other industry

4. All the solar engineers, battery engineers, grid operators and utility analysts I spoke to, people whod widely studied how you build out a renewable grid, said the same thing.

1. You cannot build a renewable grid without having flexible load customers

2. Bitcoin miners are the best flexible load customers theyve seen

3. Bitcoin mining is increasingly using energy that would have otherwise been wasted (such as solar energy at midday or wind at midnight when people didnt need it)

4. Bitcoin mining provided a path to retire all fossil fuel-based turbines needed as backups during peak load times

5. Bitcoin mining helped with maintaining the frequency and voltage regulation of the grid (which become progressively harder with every 10% of variable renewable energy you add)

6. Bitcoin mining could make power more affordable to consumers by reducing the curtailment fees that utilities otherwise had to pay to renewable operators for not taking their surplus power.

There were a host of other benefits too. But this would require some deeper analysis (and jargon) about how electrical grids work.

But really, the first two points say it all: grids built on variable renewable energy must have flexible customers who can adjust their usage according to generation supply. They must also be able to reduce their usage given minutes notice. Bitcoin miners are the only customers who provide this flexibility.

Or to put it even more bluntly: without Bitcoin mining, the renewable grid will simply not happen it will remain an ideal: Grid operators and utilities will say they are working towards it.

So what problem with renewables does Bitcoin uniquely solve?

Grid operators #1 goal is to maintain the stability of the grid. Cost-effectiveness and renewable composition is important, but not as important as stability. Thats because when grids fail, people die and grid operators lose their jobs (as recently happened during the Texas 2021 Winter Blackouts). Even with battery technology, this stability becomes progressively harder to achieve when you base your grid on variable renewable energy.

While we must move away from fossil fuel plant, coal and gas did offer one advantage over renewables: you could increase or decrease the generation of a gas plant at will. Solar and Wind dont have that flexibility. They are also highly unpredictable.

When you add inflexible and unpredictable generators such as solar and wind, unless you counterbalance this with flexible, predictable customers the entire grid will become unstable because of either under-supply or oversupply of electricity and there will be a higher risk of blackouts.

Ironically, as climate change bites, extreme weather events are becoming more common. This means that grid operators are faced with the Herculean task of trying to transition to a grid made up of variable renewable energy at a time when even the existing grid is becoming more unstable due to climate events.

Grid operators have investigated a number of other options: Hydrogen, batteries, pumped hydro, device control programs, and Demand response based on curtailing steel plants. None of them come anywhere close to the flexibility of Bitcoin miners. Even batteries are only a partial solution for reasons I cover in detail in my separate article

Bitcoins location-agnostic and time-of-day agnostic features turn out to make it the ideal way to remove most of the worlds atmospheric methane caused by human intervention too, but thats another story.

In summary: here are some quotes directly from some of the key players.

Never in my wildest dreams would I have imagined a customer as ideal as Bitcoin miners [Utility Scale Wind Operator]

I started off researching batteries as a solution to the intermittency of solar. I soon realized that without another offtaker for surplus power, batteries were incomplete. After testing a number of possible offtakers, I realized the that best one by far was Bitcoin Mining. [Sam Kivi, Solar Engineer]

We can use that cryptocurrency to find a home for more solar and more wind to come to our grid. Then they reduce consumption when we need that power for other customers. So its a great balancing act. [Brad Jones, Interim CEO, ERCOT (The Grid Operator for Texas)]

A big component of how we get [to our 2050 renewable grid goal] is new demand response strategies. And Bitcoin mining is different because you can reduce demand in minutes to the exact level you need with pinpoint precision. You just dont see that level of flexibility or response in these legacy (demand response) programs. [lead analyst, major US Electrical Utility]

So, there you have it. It wasnt what I was expecting to find. I had to put aside everything I thought I knew about Bitcoin. The more I go through life, the more I realize that until youve looked deeply into something, youre not in a position to judge it.

A deeper look at Bitcoin reveals a surprising truth. Bitcoiners sometimes despair that the mainstream media narrative does not take this deeper look. I would encourage these Bitcoiners to not be concerned. Every novel disruptive technology gets attacked because, well, it disrupts some people who do not want to be disrupted.

Meanwhile behind the scenes, Bitcoin is enabling one of the single most important transitions of a generation: the transition to the renewable grid. Sooner or later this truth will become so undeniable that Bitcoin detractors will be forced to choose a different attack vector. In the meantime, as an environmentalist, I could not be more delighted that we have Bitcoin in our world.

There is a phrase in the climate movement: the perfect is the enemy of the good. Solar isnt perfect but its good. So is the case for Wind. For Bitcoin also, its in the same club: not perfect, but good. Bitcoin offers us a practical way to build out the renewable grid at a time were in a footrace against a fast-warming world.

Daniel Batten is a ClimateTech investor, author, ESG analyst and environmental campaigner who previously founded and led his own tech company which exited in 2019.

Got something to say about Bitcoin and the enviroment or anything else? Write to usor join the discussion in our Telegram channel. You can also catch us on Tik Tok, Facebook, or Twitter.

DisclaimerAll the information contained on our website is published in good faith and for general information purposes only. Any action the reader takes upon the information found on our website is strictly at their own risk.

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Bitcoin: Why Environmentalists Need to Relax, It's Better Than You Think - BeInCrypto

The Pitt research community will celebrate the Dickson Prize in Medicine winners for 2020, 2021 and 2022 with the the first-ever Dickson Prize Day on July 19.

The Dickson Prize in Medicine is the most prestigious honor given by the Pitt School of Medicine. It has been given out annually since 1971 to an American biomedical researcher who has made significant, progressive contributions to medicine. The award consists of a specially commissioned medal, a $50,000 honorarium and an invitation to present a seminal lecture at Pitt. The winners for the past two years were unable to travel to campus because of the pandemic.

For the Dickson Prize Day, the past three years winners will give in-person talks to the Universitys research community, followed by talks from Pitt faculty whose work complements that of the Dickson Prize recipients.

Pitt faculty panelists include Warren Ruder, Vaughn Cooper, Alexander Deiters, Alison Morris, Toren Finkel, Arjumand Ghazi, Aditi U. Gurkar, Andrey A. Parkhitko, Kay Brummond, Robert Ferris and JoAnne L. Flynn.

The event will be from 8 a.m. to 5:15 p.m. July 19 in the University Club, with a reception to follow. All events also will be livestreamed.Register now.

Carolyn Bertozzi,the Dickson Prize honoree for 2022, will give a talk, Therapeutic Opportunities in Glycoscience. Bertozzi is a professor of chemistry at Stanford University.

Bertozzis research interests span the disciplines of chemistry and biology, with an emphasis on studies of how sugar molecules on cell surfaces are important contributors to diseases like cancer, inflammation and bacterial infection. Her lab has identified ways to modify these sugar molecules through bioorthogonal chemistry a method that employs chemical reactions that do not interfere with normal cellular processes. This approach has allowed her to develop new therapeutic approaches to treat many diseases, including most recently in the field of cancer immunotherapy.

In addition to her research, Bertozzi works actively to translate her science into new therapies. She has cofounded several startups, including Redwood Bioscience, Enable Biosciences, InterVenn Biosciences, OliLux Biosciences and Lycia Therapeutics.

Cynthia Kenyon, the 2021 Dickson Prize winner, will discuss The Plasticity of Aging. Kenyon is vice president of aging research at Calico Life Sciences, an American Cancer Society professor, and emeritus professor of biochemistry and biophysics at the University of California-San Francisco.

In 1993 as a faculty member at UCSF, Kenyon discovered that a single gene mutation could double the lifespan of healthy roundwormsa finding that sparked an intensive study of the molecular biology of aging. Her research showed that the aging process is not random and haphazard as previously thought but, instead, is subject to active genetic regulation. Her work led to the realization that a hormonal network influences the rate of aging in many organisms, possibly including humans.

Since then, Kenyon and her lab members discovered a variety of genes that influence aging by coordinating diverse processes that protect cells and tissues. In addition, Kenyon and her team found that different kinds of tissues work together to control the pace of the aging process, and that individual neurons and germ cells can control an animals lifespan.

James J. Collins, 2020 Dickson Prize honoree, will give a talk on Harnessing Synthetic Biology and Deep Learning to Fight Pathogens. Collins is the professor of medical engineering and science and professor of biological engineering at the Massachusetts Institute of Technology. He also is affiliated faculty with theBroad Instituteof MIT and the Wyss Institute at Harvard University.

Using engineering principles to design and construct synthetic gene networks, he was one of the first to harness the biochemical and biophysical properties of nucleic acids and proteins to create biological circuits. A seminal 2000 publication in Nature describing the successful creation of a bistable, synthetic gene switch inEscherichia colihas been cited more than 4,000 times and marks the arrival of an important new discipline in biomedicine.

Collins later demonstrated that synthetic gene networks could be linked with a cells genetic circuitry as a regulatory mechanism to create programmable cells for biomedical applications.More recently, Collins has created engineered microbes and whole-cell biosensors to serve asin vivodiagnostics and therapeutics. One innovative platform that he and colleagues developedembeds freeze-dried, cell-free synthetic gene networks onto paperand other materials with a wide range of potential clinical and research applications.

The resulting materials contain properties of a living cell, are stable at room temperature and can be activated by simply adding water.Collins work on freeze-dried, cell-free synthetic biology has established a platform for a new class ofrapid, programmablein vitrodiagnosticsfor emerging pathogens, including drug-resistant bacteria and viruses.Collinsand his team currently are developing a rapid self-activatingCOVID-19 face mask as a wearable diagnostic.

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Dickson Prize Day will celebrate past three winners - University Times