Category Archives: Cell Biology

Cell Biology

Less than 10% of people in Britain are immune to coronavirus. There’s no room for mistakes – The Guardian

The lockdown approach to combating Covid-19 has been undeniably effective. The surge in cases was stopped, the NHS was not overwhelmed, and many deaths were prevented. At the Francis Crick Institute, we could see the dramatic effect on cases, as weve been testing for Sars-CoV-2 to support our local hospitals. When we ran our first samples, at the peak of the first wave, nearly half were positive. Now we see perhaps one or two positive samples in a thousand.

But its not quite a fair comparison. Our earliest samples were from symptomatic self-isolating healthcare workers and we immediately realised that many other colleagues with no symptoms, or milder symptoms, would not be self-isolating. That meant they might be transmitting the virus. After a very regrettable delay, we persuaded our colleagues that it would be of critical importance to test asymptomatic healthcare workers too. One of many blunders in the first phase of the UKs response was to allow substantial transmission within hospitals and care homes.

I dont wish to dwell on past mistakes. When Boris Johnson recovered sufficiently to address the nation on 10 May, he outlined a new approach: suppressing this virus, keeping R below 1. The following day, flanked by Chris Whitty and Patrick Vallance, he emphasised this message again. I was delighted. Finally, we were pursuing the correct strategy, the one adopted early on by Hong Kong, Taiwan, South Korea, New Zealand the strategy that Sage advice had hitherto failed to identify. An acquaintance responded somewhat sardonically to my jubilation that this was exactly right with, Yes, in the sense that score more goals than the other team is exactly the right strategy for winning at football. Hes not a scientist, but a freelance singer; you can imagine how the lockdown has affected his income.

We now have the right mindset, but the challenge confronting Britain is greater than that faced by the countries that locked down early. To extend my friends analogy, weve been on the pitch with 11 playmakers nonchalantly passing the ball around, but with nobody who can either shoot or tackle. Testing, tracing and isolation is of course right, but mildly symptomatic people must be encouraged to request a test immediately. We have to turn those tests around more quickly, and we must be able to persuade their asymptomatic contacts to self-isolate. The app that could help with identification of contacts must have the broad support and trust of the public, as well as be technically beyond reproach.

Until last nights announcement by Grant Shapps, mandating masks on public transport from 15 June, we have been given only lukewarm encouragement for their use; yet just about every successful country has had mask-wearing at the heart of its success. There is good reason to believe that mask-wearing will only have a substantial effect when most people wear one. We must enact the new policies with greater efficiency if we are to succeed.

If you want to, you can extend the analogy further: as with any fan, you might complain about the owners, or want a different manager. But this isnt a game. Recent data from both Public Health England and the Office for National Statistics shows that less than 10% of the UK population is now immune to this virus. Reliable antibody tests at scale from multiple sources indicate approximately the same figure. We must discard any foolish optimism about immunological dark matter that will mysteriously prevent infection, or any other clutching at straws. The great majority of us are still susceptible to this virus, and if we allow it to transmit easily between us we will see a second wave possibly during the winter, where it may be even more deadly.

There will be mistakes, and no doubt there will still be hypocrisy and incompetence

Fundamentally, it is not just the government that has to get this right it is all of us. If we want to preserve our economy and our NHS, we must behave with personal integrity and responsibility. There will be mistakes, and no doubt there will still be hypocrisy and incompetence. These are human characteristics from which no government will ever be entirely free. What matters now is that suppressing the virus is the correct approach and that we have the means to carry it out. Matt Hancock has been upbraided by the chief government statistician for misrepresenting the number of tests, but however you count it, the capacity of 200,000 tests per day is a vast improvement on the situation in March. Credit where credit is due: its involved a huge effort from volunteer scientists at all the public health labs, hospital and academic labs and the Lighthouse labs. We can push this capacity even higher. If we can now target our testing effectively, we can loosen the lockdown and revive our economy.

If we get the next phase of our response testing, tracing and isolation wrong, our two remaining options are semi-permanent lockdown, or hundreds of thousands of deaths in an uncontrolled epidemic. Both possibilities will come with enormous economic damage, as well as a terrible cost in lives. The absolute worst thing we can do is give up hope. I wouldnt despair too much about pictures of crowds. The virus transmits less well outdoors. But we should be keeping 2 metres apart, and its irresponsible not to for any reason, even for highly justified protests. We cannot afford to mess this up.

I shall be supporting the government over testing and tracing, and helping to do all I can to make it as efficient as possible. I shall download the app when it becomes available, and I shall use it. I expect every government minister, and every government adviser to do the same. This would reassure me greatly that the app was safe to use. I have high confidence that recent events will have reminded key government advisers of the importance of privacy, and of the importance of leading by example.

New data on several vaccine candidates seems promising. If any prove successful, they will be deployed in record time.If we give up, we will see even more lives lost needlessly. If we keep up our collective effort, we can control this virus and prevent an overwhelming second wave.

Dr Rupert Beale heads the cell biology of infection laboratory at the Francis Crick Institute in London

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Less than 10% of people in Britain are immune to coronavirus. There's no room for mistakes - The Guardian

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.

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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

Cell Biology

[PDF] Essential Cell Biology Download Full PDF Book Download

Bruce Alberts,Dennis Bray,Karen Hopkin,Alexander D Johnson,Julian Lewis,Martin Raff,Keith Roberts,Peter Walter 2013-10-15Science

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Bruce Alberts,Karen Hopkin,Alexander D. Johnson,Martin Raff,David Morgan,Keith Roberts,Peter Walter 2018-11-19Science

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Fifth International Student Edition

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Cell Biology

Breakthrough discovery could lead to treatment of Fragile X syndrome – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Jun 2 2020

Scientists at the Hotchkiss Brain Institute (HBI), Alberta Children's Hospital Research Institute (ACHRI), and Owerko Centre at UCalgary's Cumming School of Medicine (CSM) have made a breakthrough discovery that could lead to treatment of Fragile X syndrome (FXS), the leading genetic cause of Autism Spectrum Disorder. The study, involving mouse models, shows promise of translating to treatment for people diagnosed with FXS.

FXS causes intellectual disabilities and hyperactive behaviour, usually more commonly seen in males than females. Children and adults with FXS are missing a protein vital to brain development called FMRP. Among other functions, FMRP helps develop synapses between neurons in the brain.

Dr. Raymond W. Turner, PhD, and members of his study team including Drs. Xiaoqin Zhan, PhD, Hadhimulya Asmara, PhD, and Ning Cheng, PhD, made the discovery while studying ion channels in the brain - special proteins that conduct currents through cells, enabling communication within the brain.

If I had to make an analogy, it might be akin to insulin and diabetes. With FXS, individuals are missing this protein - let's try putting it back in. In 30 minutes, the protein distributed throughout the brain, and accomplished what it's supposed to do at the single-cell level."

Dr. Raymond W. Turner, study lead, and professor in the departments of Cell Biology & Anatomy, and Physiology & Pharmacology at the CSM

Unlike injected insulin, which helps someone with diabetes control their blood sugar for a few hours, the FMRP injection helps restore protein levels in the cerebellum and brain for up to one day after the injection. "Hyperactivity was reduced for almost 24 hours," says Zhan, a postdoctoral scholar in the Turner lab. "We did one injection and we tested for it one day later, and three key proteins that are known to be in Fragile X were still at restored normal levels."

In other, unsuccessful attempts to inject mouse models with FMRP to mitigate FXS, scientists used the entire molecule. But Turner and his colleagues used a fragment of FMRP which was able to cross the blood-brain barrier. "It's not a full FMRP molecule at all but rather a fragment with important structural features and functional components that are active in doing things like controlling ion channels or the levels of other proteins," says Cheng, a research associate in the Turner lab.

In the next phase, the researchers will investigate using other parts of the FMRP molecule to mitigate cognitive disorders associated with FXS. "Unlike a lot of drug therapies where you hope you can get your drug to one specific group of cells, FMRP is expressed in just about every cell in the brain, so an all-encompassing wide-based application is what you want," says Turner.

Beyond potential treatments for FXS, the research could help develop treatments to offset behavioural symptoms characteristic of other Autism Spectrum Disorders.

The findings are published in Nature Communications.

Funding for the study was provided by the Canadian Institutes of Health Research (CIHR), Alberta Children's Hospital Foundation through ACHRI, Simons Foundation Autism Research Initiative (SFARI) Explorer grant, and fellowship support from FRAXA and Fragile X Research Foundation of Canada, the HBI and CSM Postdoctoral Fellowship programs.

This technology has a patent through Innovate Calgary, the university's knowledge transfer and business incubator centre, which continues to develop its commercial path through partnership/investment to advance this discovery as a viable treatment for patients.

The Turner lab works on the role of an ion channel complex they discovered that controls multiple functions in the cerebellum that led them to look at the effects of losing FMRP in the knockout mouse model. The reason replacing FMRP was so effective is that it turns out to be part of the very ion channel complex the lab has been studying for 10 years.

Led by the Hotchkiss Brain Institute, Brain and Mental Health is one of six research strategies guiding the University of Calgary toward its Eyes High goals. The strategy provides a unifying direction for brain and mental health research at the university.

Source:

Journal reference:

Zhan, X., et al. (2020) FMRP(1297)-tat restores ion channel and synaptic function in a model of Fragile X syndrome. Nature Communications. doi.org/10.1038/s41467-020-16250-4.

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Breakthrough discovery could lead to treatment of Fragile X syndrome - News-Medical.Net

Cell Biology

Texas A&M Researchers Use 3D-Printed Biomaterials Laced With Stem Cells To Create Superior Bone Grafts – Texas A&M University Today

NICE ink developed by Texas A&M researchers can be used to 3D print customizable craniofacial implants.

Courtesy of Akhilesh Gaharwar

Subtle variations in the architecture of the 22 bones of the skull give each one of us a unique facial profile. So repairing the shape of skull defects, in the event of a fracture or a congenital deformity, calls for a technique that can be tailored to an individuals face or head structure.

In a new study, researchers at Texas A&M University have combined 3D printing, biomaterial engineering and stem cell biology to create superior, personalized bone grafts. When implanted at the site of repair, the researchers said these grafts will not only facilitate bone cells to regrow vigorously, but also serve as a sturdy platform for bone regeneration in a desired, custom shape.

Materials used for craniofacial bone implants are either biologically inactive and extremely hard, like titanium, or biologically active and too soft, like biopolymers, said Roland Kaunas, associate professor in the Department of Biomedical Engineering. In our study, we have developed a synthetic polymer that is both bioactive and mechanically strong. These materials are also 3D printable, allowing custom-shaped craniofacial implants to be made that are both aesthetically pleasing and functional.

A detailed report on the findings was published online in the journalAdvanced Healthcare Materialsin March.

Each year, about 200,000 injuries occur to bones of the jaw, face and head. For repair, physicians often hold these broken bones in place using titanium plates and screws so that surrounding bone cells can grow and form a cover around the metal implant. Despite its overall success in aiding bone repair, one of the major drawbacks of titanium is that it does not always integrate into bone tissue, which can then cause the implant to fail, requiring another surgery in advanced cases.

Thus, biocompatible polymers, particularly a type called hydrogels, offer a preferable alternative to metal implants. These squishy materials can be loaded with bone stems cells and then 3D printed to any desired shape. Also, unlike titanium plates, the body can degrade hydrogels over time. However, hydrogels also have a known weakness.

Although the pliability of hydrogel-based materials makes them good inks for 3D bioprinting, their softness compromises the mechanical integrity of the implant and the accuracy of printed parts, said Akhilesh Gaharwar, associate professor in the Department of Biomedical Engineering.

To increase the stiffness of the hydrogel, the researchers developed a nanoengineered ionic-covalent entanglement or NICE recipe containing just three main ingredients: an extract from seaweed called kappa carrageenan, gelatin and nanosilicate particles that both stimulate bone growth and mechanically reinforce the NICE hydrogel.

First, they uniformly mixed the gelatin and kappa carrageenan at microscopic scales and then added the nanosilicates. Gaharwar said the chemical bonds between these three items created a much stiffer hydrogel for 3D bioprinting with an almost eight-fold increase in strength compared to individual components of NICE bioink.

Next, they added adult stem cells to 3D parts printed with NICE ink and then chemically induced the stem cells to convert into bone cells. Within a couple of weeks, the researchers found that the cells had grown in numbers, producing high levels of bone-associated proteins, minerals and other molecules. In aggregate, these cell secretions formed a scaffold, known as an extracellular matrix, with a unique composition of biological materials needed for the growth and survival of developing bone cells.

When the scaffolds are fully developed, the researchers noted that the bone cells could be removed from the scaffold and the hydrogel-based implant can then be inserted into the site of skull injury where the surrounding, healthy bones initiate healing.Over time, the 3D printed scaffolds biodegrade, leaving behind a healed bone in the right shape.

The idea is to have the bodys own bone repair machinery participate in the repair process, Kaunas said. Our biomaterial is enriched with this regenerative extracellular matrix, providing a fertile environment to naturally trigger bone and tissue restoration.

The researchers said that the 3D-printed scaffolds provide a strong structural framework that facilitates the attachment and growth of healthy bone cells. Also, they found that developing bone cells penetrate through the synthetic material, thereby increasing the functionality of the implant.

Although our current work is focused on repairing skull bones, in the near future, we would like to expand this technology for not just craniomaxillofacial defects but also bone regeneration in cases of spinal fusions and other injuries, Kaunas said.

Other contributors to this study include Candice Sears, Eli Mondragon, Zachary Richards, Nick Sears and David Chimene from the Texas A&M Department of Biomedical Engineering; and Eoin McNeill and Carl A. Gregory from the Texas A&M Health Science Center.

This research is funded by the National Institutes of Health and the National Science Foundation.

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Texas A&M Researchers Use 3D-Printed Biomaterials Laced With Stem Cells To Create Superior Bone Grafts - Texas A&M University Today