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Cell Biology

Power Electronics Products of the Week (5/31 – 6/6) – Electronic Design

Unless youre involved in cellular-biology research, you may not know about electroporation, which is a powerful yet basic method for delivering small molecules (RNA, DNA, drugs) across cell membranes by application of an electrical field. Its used in situations such as genetic engineering of cells related to drug- and DNA-based vaccine delivery, whereby a tool called an electroporator applies a jolt of electricity to temporarily open cell walls.

(Technical aside for non-biology-lab audience: One of the roles of a cell membrane is to serve as a protective border, isolating the inner workings of a living cell from the outside environment. But with a brief jolt of electricityelectroporationthat membrane will temporarily open and allow foreign molecules to flow in. This process has been used for decades in molecular biology labs for tasks ranging from bacterial detection to genetic engineering.)

Quality test equipment and tools can be expensive, even for relatively simple ones such as electroporators, which deliver a controlled, high-voltage spark and can cost hundreds or even thousands of dollars. To enable smaller labs and schools to do experiments, a team at Georgia Institute of Technology (better known as Georgia Tech) developed a simple, inexpensive, handheld electroporator dubbed the ElectroPen, inspired by and derived from a common household piezoelectric stove/barbecue lighter (Fig. 1).

1. Shown is a common butane lighter (left) from which researchers obtained a piezoelectric component used in the ElectroPen (right)an inexpensive electroporator that has a 3D-printed case. (Source: Georgia Tech)

Unlike commercial units that require batteries or an ac power source, this electroporator is self-powered by a piezoelectric crystal, thus reducing cost and complexity. It delivers repeatable exponentially decaying pulses of about 2,000 V in 5 ms.

This electroporator wasnt a one-time hack where the objective was simply to successfully repurpose the lighter to another role and then conclude good enough, now were done. Instead their project encompassed upfront material analysis including measurement of various piezoelectric crystals, performance tests like assessing consistency of applied force and resultant voltage output, and even issues of manufacturability at the Georgia Tech location and independent sites (Fig. 2). In addition to electrical and mechanical evaluations at the bench, they also used their device successfully for its intended electroporation experiments.

2. ElectroPen platform: (a) Design of the 3D-printed low-cost electroporation device along with a depiction of its size scale, demonstrating portability. The device is operated simply by pressing down the toggle to trigger the piezoelectric mechanism, resulting in electrical discharge. (b) Design of the alternative electroporation millifluidic channel. The millifluidic-channel design consists of two blocks (shown here in acrylic) covered with aluminum tape to act as electrodes and placed on a base with a gap distance of 0.1 cm. The millifluidic channel can be built out of other materials as an alternative for industrial equivalents. (c) Depiction of the origin of the piezoelectric ignition mechanism found within the common stove lighter. The inset is the striker/piezoelectric mechanism of the lighter. The region with the red cap consists of a metal housing encasing the piezoelectric crystal. The middle black region consists of the spring-latch mechanism that strikes the crystal. The bottom black region (rightmost) consists of a wedge thats the origin for user-applied force and triggers the spring mechanism. The toggle on a lighter directly exerts a force on this mechanism to produce a spark. (d) Illustration of the general protocol for using the ElectroPen system. The cellular suspension is added to the gap in the millifluidic channel, after which the ElectroPen is connected and pressed to trigger a voltage potential. The cell suspension is then recovered in Luria Bertani broth (a commonly used nutritionally rich medium for culturing bacteria) and plated. (e) Illustration of the individual components of the 3D-printed ElectroPen platform and custom millifluidic channel. (Source: Georgia Tech)

For example, the team tested several different lighter crystals to find ones that produced a consistent voltage using a spring-based mechanism with a 1000-frame/s camera to study the device mechanics in slow motion (Fig. 3). The final bill of materials (BOM) included copper-plated wire, heat-shrink wire insulation, and aluminum tape. To hold it all together, the researchers designed a 3D-printed casing that also serves as its activator. With all of the parts on hand, the device can be assembled in 15 minutes.

3. Spring-latch mechanisms for repeatable generation of high-voltage pulses. (a) Image of the striking mechanism (hammer action) found within the piezo igniter in a lighter (arrow indicates location of crystal) (i). The parts include, from top to bottom, metal conductor (gold-colored region) housing the piezoelectric crystal, springs, hammer, release spring, and geometrical latch (ii). The presence of two springs is to decouple the loading and release phase for consistent voltage output. (b) Images of the hammer and PZT crystal. The circular surface area of the hammer comes into direct contact with a pin that strikes the piezoelectric crystal, generating a voltage through the piezoelectric effect. (c) Snapshots from high-speed video illustrating the position of the hammer during the loading, latch-release, and relaxation phases (i). Free-body diagram indicating movement of each part through each phase of the hammer action, including activation and deactivation of spring forces (ii). (d) Plot of displacement of the hammer and the lower case as a function of time obtained using high-speed image video. (e,f,g) Zooming into the dynamics of the hammer during the latch-release phase reveals that the hammer achieves a peak velocity of 8 ms1 in 0.5 m/s, which corresponds to an acceleration of 30,000 m/s2. The explosive acceleration results in a 10-N force (mass of hammer is 0.3 grams) exerted over a tiny area of the PZT crystal. (Source: Georgia Tech)

Noted M. Saad Bhamla, assistant professor in Georgia Techs School of Chemical and Biomolecular Engineering, One of the fundamental reasons this device works is that the piezoelectric crystal produces a consistently high voltage, independent of the amount of force applied by the user. Our experiments showed that the hammer in these lighters is able to achieve acceleration of 3,000 gs, which explains why it is capable of generating such a high burst of voltage.

As a final confirmation of the designs practicality, they shared the design files, sample protocols, and digital instructions with research teams at other institutions, who were then able to build and use their own low-cost, DIY electroporators.

A detailed schematic, BOM, links to component sources, assembly instructions, and related documentation for the ElectroPen device project are in their published paper or being made available along with the files necessary for creating a 3D-printed enclosure. The paper ElectroPen: An ultra-lowcost, electricity-free, portable electroporator, published in PLOS Biology, closes with a realistic assessment of the capabilities and limitations of this device compared to commercial ones. The Supplemental Information available via the same link also includes numerous text and video files covering design, test, and evaluation. The project was supported by the National Science Foundation and the National Institutes of Health.

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Power Electronics Products of the Week (5/31 - 6/6) - Electronic Design

Cell Biology

Cells inside Cells: The Bacteria That Live in Cancer Cells – ETHealthworld.com

In a research conducted by Dr. Ravid Straussman's supported by the Roel C. Buck Career Development Chair and the European Research Council.

Dr. Ravid Straussman stated that cancer cells are comfy havens for bacteria. The conclusion arise from a rigorous study of over 1,000 tumor samples of different human cancers. The study, headed by researchers at the Weizmann Institute of Science, found bacteria living inside the cells of all the cancer types from brain to bone to breast cancer and even identified unique populations of bacteria residing in each type of cancer. The research suggests that understanding the relationship between a cancer cell and its mini-microbiome may help predict the potential effectiveness of certain treatments or may point, in the future, to ways of manipulating those bacteria to enhance the actions of anticancer treatments. The findings of this study were published in Science.

Dr. Ravid Straussman of the Institutes Molecular Cell Biology Department had, several years ago, discovered bacteria lurking within human pancreatic tumor cells; these bacteria were shown to protect cancer cells from chemotherapy drugs by digesting and inactivating these drugs. When other studies also found bacteria in tumor cells, Straussman and his team wondered whether such hosting might be the rule, rather than the exception. To find out, Drs. Deborah Nejman and Ilana Livyatan in Straussmans group and Dr. Garold Fuks of the Physics of Complex Systems Department worked together with a team of oncologists and researchers around the world. The work was also led by Dr. Noam Shental of the Mathematics and Computer Science Department of the Open University of Israel.

Ultimately, the team would produce a detailed study describing, in high resolution, the bacteria living in these cancers brain, bone, breast, lung, ovary, pancreas, colorectal and melanoma. They discovered that every single cancer type, from brain to bone, harbored bacteria and that different cancer types harbor different bacteria species. It was the breast cancers, however, that had the largest number and diversity of bacteria. The team demonstrated that many more bacteria can be found in breast tumors compared to the normal breast tissue surrounding these tumors, and that some bacteria were preferentially found in the tumor tissue rather than in the normal tissue surrounding it.

The team also reported that bacteria can be found not only in cancer cells, but also in immune cells that reside inside tumors. Some of these bacteria could be enhancing the anticancer immune response, while others could be suppressing it a finding that may be especially relevant to understanding the effectiveness of certain immunotherapies, says Straussman. Indeed, when the team compared the bacteria from groups of melanoma samples, they found that different bacteria were enriched in those melanoma tumors that responded to immunotherapy as compared to those that had a poor response.

Straussman thinks that the study can also begin to explain why some bacteria like cancer cells and why each cancer has its own typical microbiome: The differences apparently come down to the choice of amenities offered in each kind of tumor-cell environment. That is, the bacteria may live off certain metabolites that are overproduced by or stored within the specific tumor types. For example, when the team compared the bacteria found in lung tumors from smokers with those from patients who had never smoked, they found variances. These differences stood out more clearly when the researchers compared the genes of these two groups of bacteria: Those from the smokers lung cancer cells had many more genes for metabolizing nicotine, toluene, phenol and other chemicals that are found in cigarette smoke.

In addition to showing that some of the most common cancers shelter unique populations of bacteria within their cells, the researchers believe that the methods they have developed to identify signature microbiomes with each cancer type can now be used to answer some crucial questions about the roles these bacteria play: Are the bacteria freeloaders on the cancer cells surplus metabolites, or do they provide a service to the cell? At what stage do they take up residence? How do they promote or hinder the cancers growth? What are the effects that they have on response to a wide variety of anticancer treatments?

Tumors are complex ecosystems that are known to contain, in addition to cancer cells, immune cells, stromal cells, blood vessels, nerves, and many more components, all part of what we refer to as the tumor microenvironment. Our studies, as well as studies by other labs, clearly demonstrate that bacteria are also an integral part of the tumor microenvironment. We hope that by finding out how exactly they fit into the general tumor ecology, we can figure out novel ways of treating cancer, Straussman says.

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Cells inside Cells: The Bacteria That Live in Cancer Cells - ETHealthworld.com

Cell Biology

Follica Announces Positive Feedback From End of Phase 2 Meeting With FDA for Its Lead Program to Treat Male Androgenetic Alopecia – BioSpace

BOSTON--(BUSINESS WIRE)-- Follica, Inc. (Follica), a biotechnology company developing a regenerative platform designed to treat androgenetic alopecia, epithelial aging and other related conditions, today announced positive feedback from a meeting with the U.S. Food and Drug Administration (FDA) as the company prepares to advance its lead program into Phase 3 development following a successful safety and efficacy optimization study for the treatment of hair loss in male androgenetic alopecia announced in December 2019.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20200603005934/en/

Follicas approach, which is designed to stimulate the growth of new follicles and new hair, is being developed as a potential new option for the millions of people seeking treatments to grow new hair. (Graphic: Business Wire)

Follica plans to launch its Phase 3 program this year. Overall, approximately 280 patients will be enrolled, with efficacy assessed against two co-primary endpoints: visible (non-vellus) hair count and patient-reported outcomes on a pre-established scale. The randomized, controlled, double-blinded studies will be conducted in multiple centers across the U.S. A maximal use study to further understand the pharmacokinetics of the treatment will be conducted in parallel. The trial design is consistent with feedback from the FDA during the End of Phase 2 meeting.

In the U.S. alone, 47 million men are affected by progressive hair loss caused by androgenetic alopecia, a condition that is largely unresolved today, leaving many dissatisfied with the current available treatments and looking for a new alternative. Our recent safety and optimization study points to a new level of effect, enabled by our proprietary approach, which stimulates the growth of new follicles and new hair, said Jason Bhardwaj, chief executive officer of Follica. Were grateful to the FDA for their guidance as we prepare for our pivotal program, and we look forward to advancing the development of our treatment regimen, which has demonstrated strong potential to address the current need for those who seek treatment for androgenetic alopecia.

Follicas approach is based on generating an embryonic window in adult scalp cells via a series of short office-based treatments with its proprietary Hair Follicle Neogenesis (HFN) device. The scalp treatments, which last just a few minutes, stimulate stem cells and enable the growth of new hair follicles. A topical drug is then applied to enhance efficacy by growing and thickening new hair follicles and hair on the scalp.

Follica reported topline results from its safety and optimization study in December 2019. That trial was designed to select the optimal treatment regimen using Follicas proprietary HFN device in combination with a topical drug and successfully met its primary endpoint. The selected treatment regimen demonstrated a statistically significant 44% improvement of visible (non-vellus) hair count after three months of treatment compared to baseline (p < 0.001, n = 19). Across all three treatment arms, the overall improvement of visible (non-vellus) hair count after three months of treatment was 29% compared to baseline (p < 0.001, n = 48), reflecting a clinical benefit across the entire trial population and a substantially improved outcome with the optimal treatment regimen. Additionally, a prespecified analysis comparing the 44% change in visible (non-vellus) hair count to a 12% historical benchmark set by approved pharmaceutical products established statistical significance (p = 0.005).

In addition to the safety and optimization study, Follica has validated its approach in prior clinical studies using prototype HFN devices with different treatment parameters and therapeutic compounds. Follicas translational work builds on research by George Cotsarelis, M.D., who isolated and characterized the expression pattern of stem cells from a critical region of the follicle. An expert in epithelial stem cell biology, Dr. Cotsarelis is chair of the department of dermatology at the University of Pennsylvania and a co-founder of Follica.

About Androgenetic Alopecia Androgenetic alopecia represents the most common form of hair loss in men and women, with an estimated 90 million people who are eligible for treatment in the United States alone. Only two drugs, both of which have demonstrated a 12% increase of non-vellus hair count over baseline for their primary endpoints, are currently approved for the treatment of androgenetic alopecia1. The most effective current approach for the treatment of hair loss is hair transplant surgery, comprising a range of invasive, expensive procedures for a subset of patients who have enough donor hair to be eligible. As a result, there remains a significant need for safe, effective, non-surgical treatments to grow new hair.

About Follica Follica is a biotechnology company developing a regenerative platform designed to treat androgenetic alopecia, epithelial aging and other related conditions. Founded by PureTech (LSE:PRTC), a co-inventor of the current platform, and a group of world-renowned experts in hair follicle biology and regenerative medicine, Follicas experimental treatment platform has been shown to stimulate the development of new hair follicles and hair in three previously conducted clinical studies. The companys proprietary treatment is designed to induce an embryonic window via a device with optimized parameters to initiate hair follicle neogenesis, the formation of new hair follicles from epithelial (skin) stem cells. This process is enhanced through the application of a topical compound. Follica completed a safety and efficacy optimization study in 2019, and its Phase 3 program in male androgenetic alopecia is expected to begin in 2020. Follicas technology is based on work originating from the University of Pennsylvania that has been further developed by Follicas internal program. Follicas extensive IP portfolio includes IP exclusively licensed from the University of Pennsylvania as well as Follica-owned IP.

1 Olsen EA et al, J Am Acad Dermatol. 2002 Sep;47(3):377-85Olsen EA et al, J Am Acad Dermatol. 2007 Nov;57(5):767-74. Epub 2007 Aug 29Price VH et al, J Am Acad Dermatol. 2002 Apr;46(4):517-23Kaufman et al, J Am Acad Dermatol. 1998 Oct; 39(4):578-589

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Follica Announces Positive Feedback From End of Phase 2 Meeting With FDA for Its Lead Program to Treat Male Androgenetic Alopecia - BioSpace

Cell Biology

Scientists Have Engineered Human Cells With a Squid-Like Power of Invisibility – ScienceAlert

The opalescent inshore squid has a superpower. Not only can it change the colour of its skin - which many chephalopscan do -it can also turn parts of itself invisible. Now, scientists have used this ability on human cells.

Using special proteins found in the cells of these changeling squids, researchers managed to apply them to human kidney cells. Their findings could help us to better understand various cellular mechanisms in living tissue.

"Our project centres on designing and engineering cellular systems and tissues with controllable properties for transmitting, reflecting and absorbing light," explained biomolecular engineer Atrouli Chatterjee from the University of California (UCI).

A female opalescent inshore squid with her eggs. (Brent Durand/Moment/Getty Images)

Squids aren't the only animals to make use of see-through skin. While gliding lizards (Draco sumatranus) use their skin translucency to draw attention, opalescent inshore squids (Doryteuthis opalescens) use theirs to avoid unwanted attention.

Females of this squid species can turn a white stripe along their backs from opaque white to nearly transparent. They do this using specialised cells called leucophores, which have membrane-bound particles made of reflectin proteins.

Depending on how these proteins are arranged,they can change how light is transmitted or reflected around them. And it's not a random process: Squids can alter the arrangement of these highly refractive proteins within their cells, using an organic chemical called acetylcholine.

To try this trick in human tissue, the research team genetically engineered human kidney cells to produce reflectins, which clumped together as disordered particles in the cell's cytoplasm.

"We were amazed to find that the cells not only expressed reflectin but also packaged the protein in spheroidal nanostructures and distributed them throughout the cells' bodies," said UCI biomedical engineer Alon Gorodetsky.

Using quantitative phase microscopy, the researchers showed these proteins changed the way light was scattering through the engineered cells, compared to kidney cells without reflectin.

They then exposed the reflectin-expressing cells to different levels of sodium chloride and found they could adjust the levels of light being transmitted through them, as the salt made the reflectin particles swell in size, and change how they arranged themselves.

The more salt, the more light scattered, and the more opaque the cells became. The kidney cells now had tunable light-transmitting and light-reflecting capabilities - essentially an opacity dial of sorts.

Experimental setup. The cells became more opaque after exposure to salt (bottom). (Chatterjee et al, Nat. Commun, 2020)

The reflectin's reaction to salt "bore a superficial resemblance to the acetylcholine-triggered switching of the opacity and broadband reflectance for female D. opalescens squids' leucophore-containing layers", the researchers wrote in their paper.

The team says their success lays the groundwork for incorporating other squid tricks into mammalian cells, like changing colour patterns and iridescence.

It will also allow researchers to further explore the mechanisms behind these abilities, as so far, culturing cephalopod skin cells in a lab has proved very challenging.

Possible future applications could include the ability to image entire living tissues with improved clarity - allowing us to find things that weren't apparent before. The team pointed out how similar studies on jellyfish's green fluorescent proteins led to their now popular use in fluorescence microscopy.

"Our findings may afford a variety of exciting opportunities and possibilities within the fields of biology, materials science, and bioengineering," the team concluded.

This research was published in Nature Communications.

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Scientists Have Engineered Human Cells With a Squid-Like Power of Invisibility - ScienceAlert

Cell Biology

Something in the Water: Environmental Pollutant May Be Much More Hazardous Than Previously Thought – SciTechDaily

Sometimes toxins, such as hazardous wastes and industrial byproducts, seep into groundwater, the source of our drinking water. One such pollutant is perchlorate, a chemical compound used in rocket fuels, fireworks, fertilizers, and other materials. The compound is thought to contribute to health issues in humans such as hypothyroidism, the decreased production of hormones from the thyroid gland, which can impact development.

In a new study published on May 25, 2020, in the journal Nature Structural & Molecular Biology, researchers at Johns Hopkins Medicine, Vanderbilt University and the University of California, Irvine, report on the mechanism that perchlorate uses to impact and damage normal functioning of the thyroid gland.

The findings, they say, suggest that an acceptable safe concentration of perchlorate in drinking water is 10 times less than previously thought.

The researchers focused on how perchlorate blocks a main route by which iodide, the negatively charged form of the element iodine, enters thyroid cells. Iodide helps the thyroid make hormones that are essential to the bodys regulation of metabolism, temperature and other important functions.

Perchlorate, a chemical compound used in rocket fuels (such as the Space Shuttles solid propellant seen here during the programs final launch in 2011) and other materials, may be a more hazardous pollutant than previously thought. Credit: M.E. Newman, Johns Hopkins Medicine, using NASA and public domain images.

Thyroid cells control the incoming flow of iodide by using a protein channel called the sodium/iodide symporter, also known as the Na+/I- symporter or NIS. Like other cellular transport systems, a lock-and-key approach is used to move iodide, with NIS acting as the lock and sodium as the key. Sodium fits into NIS at two binding sites to unlock the channel, enabling iodide to pass through and accumulate inside a thyroid cell.

The team, led by L Mario Amzel, Ph.D., professor of biophysics and biophysical chemistry at the Johns Hopkins University School of Medicine, and Vanderbilt University researcher Nancy Carrasco, M.D., determined that perchlorate blocks the channel by latching onto the NIS protein and changing its shape. Less sodium binds to the misshaped channel, thereby significantly lowering the amount of iodide that can be moved inside thyroid cells.

The researchers studied how varying concentrations of perchlorate affects iodide transport by first growing thyroid cells that expressed the gene SLC5A5, which encodes the instructions for building NIS channels. Next, perchlorate and radioactive iodine were placed outside of some of the cells and just radioactive iodine outside the others. Finally, the researchers tracked how much glowing iodide was allowed to enter the cells in both groups. They found that there was much less iodide inside thyroid cells treated with perchlorate than in untreated ones, even at very low concentrations of the chemical.

In May 2020, the U.S. Environmental Protection Agency (EPA) ruled not to place regulations on the amount of perchlorate that can be allowed in drinking water. The findings from the new study strongly suggest that this environmental pollutant is more hazardous than previously thought, raising serious concern about the decision.

We hope that these findings will prompt the EPA to change its mind, Amzel says.

Reference: Allosteric regulation of mammalian Na+/I symporter activity by perchlorate by Alejandro Llorente-Esteban, Ran W. Manville, Andrea Reyna-Neyra, Geoffrey W. Abbott, L. Mario Amzel and Nancy Carrasco, 25 May 2020, Nature Structural & Molecular Biology.DOI: 10.1038/s41594-020-0417-5

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Something in the Water: Environmental Pollutant May Be Much More Hazardous Than Previously Thought - SciTechDaily

Cell Biology

How California Can Lead The Global Bioeconomy: A Conversation With Zymergen CEO Josh Hoffman – Forbes

Zymergen has produced a billion pounds of bio-based products, and theyre just getting started. CEO ... [+] and co-founder Josh Hoffman sat down with me to talk about the future of the bioeconomy.

In their 2019 book The Making of a Democratic Economy, Marjorie Kelly and Ted Howard pose a provocative question: Why not use the U.S. Federal Reserve System to buy up all the nations oil companies and close them down? The goal: to dramatically decelerate climate change and jump-start policy and investment in sustainable energy.

This may sound like an absurd idea with a hefty check (the top ten U.S. oil companies are valued at about $500 billion). However, the U.S. government has committed to spending over $6 trillion on the coronavirus crisis, and that number could go higher. What if we spent the same amount to prevent the climate crisis?

I sat down with Josh Hoffman, the CEO and co-founder of Zymergen, to ask him this and other questions to get his perspective on the emerging bioeconomy. If you havent heard of Zymergen before, it manufactures microbes for Fortune 500 companies. Utilizing a combination of biology, machine learning, and automation, its products range from materials (see my earlier article about the novel material Hyaline used in the electronics industry) to agricultural solutions, to personal care products.

Can we talk about the oil industry? What do you think of the bold idea to buy out the industry in California and pay them to simply leave the oil in the ground?

Its important to take a historical perspective. Human welfare has increased incredibly because of the ingenuity of cracking and using hydrocarbons. Modern materials, modern medicine - all these things are outgrowths of the petrochemical industry. I think its important to recognize that.

Its also important to recognize that these advances in human welfare have also come with a list of problems we now need to solve. For example, increased agricultural productivity means that we can feed the world, but it also means that many people are now morbidly obese, and the amount of people suffering from diabetes has increased to a point at which it never was before. And there has to be a fierce urgency to solve these problems now.

Our planet is on fire. Climate change is the biggest existential threat. And in a moment like this, with COVID-19, it is easy to forget all of these problems.

I love the poetry of keeping the oil in the groundit's a wonderful idea to think about. But it is wholly impractical. So many things we need and use today comes from oil and gas, and I think we need to figure out a transition. The way we think about transition at Zymergen is to give people better products.

Here is a real lesson from the first-generation biofuels companies: the market is not going to pay you for the sake of being green. But they will pay for something better. So our approach is, How do we make things that are better and disrupt the economics of petroleum?

HyalineZymergens new bioelectronic materialseems like a good example of this. Can you tell me why its better than its conventional counterparts?

First, lets compare petrochemistry to biology. If you crack a hydrocarbon, you will get around 15 intermediates, maybe a couple of hundred base monomers, and a limited number of polymers.

Biology gives you orders of magnitude more, and those chemicals look different.In manufacturing, think of petrochemistry like a black & white silent film, and biology like multichannel, live streaming, interactive entertainment. Its a complete step-change in not just the quantity but also the quality of products you can make. Biology lets you solve problems we couldn't even imagine solving with conventional chemistry.Its the most powerful manufacturing platform on the planet.

Now, lets look at Hyaline. Its a colorless film that is used to make electronics like smartphones, laptops, watches, and televisions. It is a fundamental product innovation in a $10 to $12 billion market that hasnt seen this kind of innovation in 50 years. Its a better product that allows a greater density of printed flexible circuits, better touchscreens, and more resilient products with superior properties, in one of the most demanding markets on the planet. By starting with biology, we are able to do things that were unimaginable before.

So Hyaline is a completely new molecule that you designed?

Hyaline is the film, and the film is based on a proprietary monomer. But again, if I show up at a cell phone manufacturer and tell them I have an amazing biology, theyll say they dont care. Even if I say I have an amazing monomer or polymer, they wont necessarily care. But if I have a film that solves a problem, then I am meeting the customer where they are. We have to solve their problems. For anyone to make money on a product, you have to sell them something that solves a problem. No one cares about the molecule itself, or whether its made with biology or not. They care about the problems it solves. Thats how biology will disrupt petroleum.

If you were on Gavin Newsom's task force looking for medium to long term policies to set California on the right path for the next 50 years, what policy recommendations would you make to him?

First, I would continue investment in the UC (University of California) system. The Bay Area has top universities that are truly world-class and you cannot underestimate the value of that. I think it is important that the state does not lose its distinctiveness that comes from having these top universities.Another might be a state-mandated purchasing of bio-based goods, like the USDA BioPreferred program. The goal of a BioPreferred Program is to create market incentives that encourage manufacturers to use sustainable goods in their supply chains, and also spur innovation by reducing market uncertainty. Imagine that the Department of Education needs to buy carpets. Where theres a bio-based carpet that performs as well or better than conventional carpet at a comparable price, the BioPreferred Program would mandate purchasing the bio-based product. This would be a simple, effective way to help establish the biomanufacturing industry. A California BioPreferred policy is something I would love to see, it sounds like a wonderful idea.Third is housing costs. It is very expensive to live in this area and hard to get people to come work here. I especially worry about young people being able to come and work here.

What do you think of Marc Andreessen's piece, It's Time to Build, and the role of the VC community in the bioeconomy specifically?

I think there is a tension between what Marc writes and reality. VCs look for a five-year path to liquidity. Five years to invest, five years of return, and one year of extensions, so eleven years at most. That timeline is tough for some of the markets that Marc is talking about. I think its an admirable spirit, but I d0nt know what you do with it.

If you want to build stuff, you need to know something about the real economy. You need to make sure you have time horizons that allow you to invest, and that youre not necessarily investing against previous patterns, like seeking the Uber of haircuts or the SAS of human resources. There is a wall of capital out there, and we need places to put the money. But we need to get away from the recursive problem of I need to see a path to exit in five years.

Take Salesforce as an example. Marc Benioff created the most successful enterprise software company of the decade. Do you know who the VCs were? Nobody, because Marc couldnt get anybody to write the check. It was an unlikely idea with a very different model. I believe the same is true for the bioeconomy: big disruptive platforms tend to be stuff that falls outside of what mainstream venture firms do. We are all comfortable doing what others have done, but its pretty lonely to be out there doing your own thing.

What advice would you give to somebody trying to raise capital in the bioeconomy?

What we did well at Zymergen was to find ways to generate revenue early. Validate your product or service early. Also, be sure to play the long game. This is a slow and steady race. Don't hype yourself up too much and raise money on unsustainable plans.

If software is eating the world, biology is going to rebuild it. Its going to take time rebuilding the world with biology, so dont go out there saying you can do magic.

To learn more about the growing bioeconomy, read my previous articles on McKinseys $4 trillion bioeconomy report and the five sectors set to be disrupted by synthetic biology.

Follow me on twitter at @johncumbers and @synbiobeta. Subscribe to my weekly newsletters on synthetic biology. Thank you to Stephanie Michelsen and Kevin Costa for additional research and reporting in this article. Im the founder of SynBioBeta, and some of the companies that I write aboutincluding Zymergenare sponsors of the SynBioBeta conference and weekly digest heres the full list of SynBioBeta sponsors.

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How California Can Lead The Global Bioeconomy: A Conversation With Zymergen CEO Josh Hoffman - Forbes

Biochemistry

Predicting the evolution of COVID-19 to help manage future outbreaks – UBC Faculty of Medicine – UBC Faculty of Medicine

As the world prepares for future waves of COVID-19, the ability to predict mutations in the novel coronavirus even before they emerge will be essential to stopping future outbreaks.

Dr. Natalie Strynadka

UBC faculty of medicines Dr. Robert Brunham and Dr. Natalie Strynadka, together with the faculty of sciences Steven Plotkinalong with a team of commercial and academic collaboratorsare one step closer to achieving this thanks to a $1.8 million grant from the Digital Technology Supercluster COVID-19 Program, which aims to find solutions to urgent health care needs across Canada arising from COVID-19.

The project, Predicting the Evolution of COVID-19, brings together experts in artificial intelligence, computer modelling and structural biology to predict changes to SARS-CoV-2, the virus that causes COVID-19. The findings will inform the early design of effective tests, therapies and vaccines, allowing public health systems globally to prepare and ideally prevent future pandemics caused by evolving strains of the virus.

For the first six-month phase of the project, Dr. Strynadkas lab is working to generate atomic resolution experimental datausing a cutting edge biophysical toolbox including x-ray crystallography and single particle cryo-electron microscopythat will in turn help train the computational algorithms to optimally predict future mutations of the virus

We are incredibly excited about this project, and grateful to the Digital Technology Supercluster for supporting our work, says Dr. Strynadka, a professor in the faculty of medicines department of biochemistry and molecular biology. Our goal is to harness powerful computational methods to predict mutations in the SARS-CoV-2 virus. We are working to create algorithms that will hopefully keep us a step ahead of the virus and give us the ability to know where future mutations might arise.

Our goal is to harness powerful computational methods to predict mutations in the SARS-CoV-2 virus. We are working to create algorithms that will hopefully keep us a step ahead of the virus and give us the ability to know where future mutations might arise. Dr. Natalie Strynadka

Dr. Brunham, a professor in the faculty of medicines division of infectious diseases and head of the Vaccine Research Laboratory at the BC Centre for Disease Control who was involved in responding to the SARS outbreak in 2003, is lending his expertise in vaccine development.

Dr. Robert Brunham

We believe the coronavirus spike protein may very well be the basis for a vaccine for this virus, says Brunham. This work will be tremendously important in anticipating whether the virus will mutate to escape immunity generated by the vaccine.

As part of the project, Plotkins lab is designing a universal antibody therapy that the virus cant easily evade through mutation.

Given past outbreaks such as SARS and MERS, which were also caused by coronaviruses, there is no reason to assume that another pandemic wouldnt happen again, says Plotkin, a professor in the department of physics and astronomy and has held a Canada Research Chair in Theoretical Molecular Biophysics. This is a problem that is not going to go away on its own, so we have to be forward-thinking in finding solutions for it.

The Predicting the Evolution of COVID-19 project is led by Terramera, a Vancouver-based company that fuses science, nature and artificial intelligence to transform how food is grown and the economics of agriculture. Collaborating partners include D-Wave, Menten AI, Microsoft, and ProMIS Neurosciences.

See the article here:
Predicting the evolution of COVID-19 to help manage future outbreaks - UBC Faculty of Medicine - UBC Faculty of Medicine

Biochemistry

Researchers are developing portable device to detect the presence of PFAS in water – News-Medical.Net

Potentially harmful man-made chemicals used in firefighting foam and consumer products have contaminated groundwater and even private wells near military, industrial and disposal sites across the country-; including Joe Foss Field and Ellsworth Air Force Base in South Dakota.

Currently, scientists must take water and soil samples from the sites to the lab and use expensive instruments to detect the presence of per- and poly-fluoroalkyl substances, known as PFAS, said South Dakota State University chemistry and biochemistry professor Brian Logue.

"There currently is not a good way to take that technology to the field."

Logue and research scientist Randy Jackson of Seacoast Science, Inc. are developing a portable device to detect the presence of PFAS in water, sediment, and soil through a two-year, $300,000 Phase II Small Business Innovation and Research grant from the Environmental Protection Agency.

This is part of the agency's efforts to help states and communities identify and address PFAS contamination and thereby protect the nation's drinking water.

PFAS is a family of more than 3,000 chemicals used to make water- and stain-resistant fabrics, carpets, and clothing as well as nonstick cookware. They are in paints, cleaning products, some food packaging, and firefighting agents.

Some are also present in coatings for electronic components and solar panels as well as in medical devices.

The researchers are expanding the technology they developed for a portable cyanide detection device. That project was part of Jackson's doctoral work, which he completed under Logue's tutelage.

PFAS has been called "forever chemicals" because they are very stable-; they persist both in the environment and in the human body.

For most organic compounds, there are bacteria or oxidative or hydrologic chemical reactions that degrade them into less toxic compounds.However, PFAS is very difficult to degrade, so they stick around for a long time unless you actively try to degrade them."

Brian Logue, Professor of Chemistry and Biochemistry, South Dakota State University

"They are engineered to break down slowly with a half-life in water of more than 92 years," Jackson said.

"Their high water solubility makes them especially dangerous they can enter and be transported by groundwater into the drinking water supply."

Ellsworth Air Force Base near Rapid City is one of the EPA's Superfund cleanup sites, due to PFAS contamination from the foam used to extinguish aircraft fires.

In 2017, the U.S. Air Force reported that PFAS groundwater contamination had spread beyond the base into local private drinking water wells.

Last June, the City of Sioux Falls filed suit in U.S. District Court against a number of chemical companies, including 3M and DuPont, because PFAS has contaminated surface and groundwater, soil, and sediment in the portion of Joe Foss Field leased to the South Dakota Air National Guard.

Human exposure can occur through contaminated water, soil, and air. In 2007, the Centers for Disease Control and Prevention, which monitors human exposure to environmental chemicals, found 98% of Americans have detectable levels of PFAS in their blood.

The substances also accumulate in the liver and kidneys.

Scientists have just begun studying their impact on human health; however, changes in liver, thyroid, and pancreas function and hormone levels occur in animals exposed to high levels of PFAS, according to the Agency for Toxic Substances and Disease Registry.

In Phase I, which was completed last year, the researchers showed they can measure/detect PFAS in water.

"We came up with the idea to degrade PFAS to smaller components that are not as difficult to analyze, then isolate them and detect them fluorometrically like we detect cyanide in our lab," Logue explained. However, he noted, though the concept is similar, "all the details are quite a bit different."

Degrading the PFAS into smaller components is relatively easy, but selectively isolating these components from the matrix is challenging, he explained.

Furthermore, the researchers had to synthesize chemicals that would react, or fluoresce, in the presence of the smaller components.

"We found a good fluorometric agent in Phase I, did some degradations, and got some good results," Logue said. Two doctoral students are also working on the project. During Phase II, the researchers will put the proof of concept into practice.

"Now it is time to take the core technology and create a sensor to do this analysis," he added.

This will involve optimizing the process, determining exactly which chemistry to use and the time required to detect PFAS.

"We've focused so far on water, which is the easiest matrix," Logue said. "Once the sensor works well with water, there are ways to prepare soil samples to use that same technology."

Based on the near-real-time analysis, the scientists will then know whether the site warrants further assessment.

In addition, Logue sees the possibility of further applications for the sensor because industries use similar compounds.

The rest is here:
Researchers are developing portable device to detect the presence of PFAS in water - News-Medical.Net

Neuroscience

Study shows brain and stomach connections are a two-way street – Minneapolis Star Tribune

For much of the 20th century, most people thought that stress caused stomach ulcers.

But that belief was largely dismissed 38 years ago when a study, which led to a Nobel Prize in 2016, described the bacterium that generates inflammation in the gastrointestinal tract and causes peptic ulcers and gastritis.

The history of the idea that stress causes ulcers took a side step with the discovery of Helicobacter pylori, said Dr. David Levinthal, director of the University of Pittsburgh Neurogastroenterology & Motility Center. For the longest time most of the 20th century the dominant idea was that stress was the cause of ulcers until the early 1980s with discovery of Helicobacter pylori that was tightly linked to the risk of ulcers. That discovery was critical but maybe over-generalized as the only cause of ulcers.

Now in an important world first, a study co-authored by Levinthal and Peter Strick, both from the Pitt School of Medicine, has explained what parts of the brains cerebral cortex influence stomach function and how it can affect health. Our study shows that the activity of neurons in the cerebral cortex, the site of conscious mental function, can impact the ability of bacteria to colonize the stomach and make the person more sensitive to it or more likely to harbor the bacteria, Levinthal said.

The study goes far beyond ulcers by also providing evidence against the longstanding belief that the brains influence on the stomach was more reflexive and with limited, if any, involvement of the thinking brain. And for the first time, the study also provides a general blueprint of neural wiring that controls the gastrointestinal tract.

This is a very important study and a continuation of several other studies that Dr. Strick has carried out in the last few years, said Peter Sterling, professor of neuroscience in the University of Pennsylvania School of Medicine and author of the recent book, What is Health. He had no involvement in the study.

Its been traditional in biology and medicine that the internal organs are self-regulatory through the autonomic nervous system, largely independent of higher brain regions, he said. Peter Strick is a world leader in establishing evidence that internal organs are strongly modulated at the highest levels by the cerebral cortex.

Stricks previous research, for instance, showed that similar areas of the cerebral cortex also control kidney and adrenal function. That course of research now could extend to the heart, liver and pancreas to discover more about how the brain coordinates control of internal organs, said Sterling, who holds a Ph.D. in neuroscience.

Influencing the gut

The Pitt study goes even further by demonstrating that widespread and different regions of the cerebral cortex influence stomach function in different ways.

The study, published May 18 in the Proceedings of the National Academy of Sciences, describes how portions of the brains cerebral cortex including the rostral insula and medial prefrontal cortex connect with and can affect the microbiome.

That those areas of the brain also are associated with emotional control helps explain how mental activity how you think, feel and prepare to move may create an encouraging environment for Helicobacter pylori.

The sympathetic nervous system generates the fight or flight response an involuntary response that sends more blood flow rushing to the muscles and the release of hormones to boost awareness and heart rate. It also reduces blood flow for digestion during stressful or life-threatening situations.

On the other hand, the parasympathetic nervous system also produces involuntary signals that maintain regular bodily functions such as digestion, normal breathing and the routine heartbeat.

As the study now reveals, these two limbs of autonomic control over the stomach are influenced by distinct cortical networks.

When it comes to trusting your gut, it already is well-established that the stomach and gut send ascending signals to the brain in a way that influences brain function. It helps to explain how the microbiome affects brain function. But the study has found that the central nervous system both influences and is influenced by the gastrointestinal system.

What people havent understood to date, Strick said, is that the brain also has descending influences on the stomach with various parts of the brain involved in that signaling, including those areas that control movement and emotions. That helps explain how stress disrupts and why exercise improves the functioning of the GI tract.

Not trivial influences

Whats new here is the extent and range of cortical areas that influence the stomach, said Strick, the studys senior author. Those areas control the stomach as directly as cortical control of movement. These are not trivial influences.

Key to the study, which involved rats, was the use of a rabies virus to trace nerve-system pathways backward from the gut to the areas of the brain involved in signaling the microbiome. The rabies virus placed in the stomach wall hops from neuron to neuron in a direction opposite that of nerve impulses.

That identified the areas of the cerebral cortex that send signals to the stomach, allowing the researchers to map the brain network influencing the microbiome and GI tract.

As such, Levinthal said, the study serves as a foundation for studies focused on controlling stomach function with electromagnetic stimulation to potentially treat and, in time, reverse gastrointestinal disorders including inflammatory bowel syndrome and dyspepsia by restructuring the microbiome.

I think this opens up a whole new way of thinking, he said.

That motor areas of the brain also help control the GI tract explains why exercise improves digestion and makes one feel better.

Building stress resilience working on skills to arm ourselves with resilience in dealing with COVID-19, finances and job loss and how we cope with exposure to stress are something to work on, Levinthal said.

Scott Grafton, the director of the University of California Santa Barbara Brain Imaging Center among other positions, said the Pitt study, in which he was not involved, is important on three key levels.

The first expands on the longstanding belief that the gut is controlled by the brain stem and more primitive areas of the brain that generate mostly reflexive responses.

The critical missing link is where in the cortex does the thinking brain our moods and our mind have inputs into the stomach, and no one really established that before, he said.

Another links the mind and microbiome how bacteria interact with the gut and influence well-being. The third focus is the pathways that abnormal proteins, which could be involved in triggering Alzheimers and Parkinsons diseases, might use to get from the gut to the brain.

Until now, this was all speculation about the brain and how we think it influences the stomach what the connection is and where is the wiring, Grafton said. Stricks expertise is how the wiring works how the nervous system interacts with all parts of the body. We need to know the wiring.

Continued here:
Study shows brain and stomach connections are a two-way street - Minneapolis Star Tribune

Neuroscience

Neuroscience Market to Witness Heightened Growth During the Period 2020 2026 – News Distinct

CMI published a business research report on Neuroscience Market: Global Industry Analysis, Size, Share, Growth, Trends, and Forecasts 20202026. Neuroscience Market with 150+ market data Tables, Pie Chat, Graphs & Figures spread through Pages and easy to understand detailed analysis. The information is gathered based on modern floats and requests identified with the administrations and items.

The global Neuroscience Market analysis further provides pioneering landscape of market along with market augmentation history and key development involved in the industry. The report also features comprehensive research study for high growth potential industries professional survey with market analysis. Neuroscience Market report helps the companies to understand the market trends and future market prospective,opportunities and articulate the critical business strategies.

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Geographical segmentation of Neuroscience Market involves the regional outlook which further covers United States, China, Europe, Japan, Southeast Asia and Middle East & Africa. This report categorizes the market based on manufacturers, regions, type and application.

Neuroscience Market: Competitive Landscape

Leading players operating in the global Neuroscience Market include:Alpha Omega, Inc., GE Healthcare, Axion Biosystems, Inc., Siemens Healthineers, Blackrock Microsystems LLC, Femtonics Ltd., Intan Technologies, LaVision Biotec GmbH, Mediso Medical Imaging Systems, Neuralynx Inc., NeuroNexus Technologies, Inc., Newport Corporation, Plexon Inc., Noldus Information Technology, Scientifica Ltd., Sutter Instrument Corporation, Thomas Recording GmbH, and Trifoil Imaging Inc.

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The key features of the Neuroscience Market report 2019-2026 are the organization, extensive amount of analysis and data from previous and current years as well as forecast data for the next five years. Most of the report is made up from tables, charts and figures that give our clients a clear picture of the Neuroscience Market. The structure of Neuroscience Market by identifying its various segments and sub-segments to help understanding the report.

Neuroscience Market Research Report gives current competitive analysis and also valuable insights to clients/industries, which will assist them to prepare a new strategy to expand or penetrate in a global Neuroscience Market.

As the report proceeds further, it covers the analysis of key market participants paired with development plans and policies, production techniques, price structure of the Neuroscience Market. The report also identifies the other essential elements such as product overview, supply chain relationship, raw material supply and demand statistics, expected developments, profit and consumption ratio.

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Neuroscience Market to Witness Heightened Growth During the Period 2020 2026 - News Distinct