Category Archives: Cell Biology

Cell Biology

Immune cell type in breast ducts points to better treatment of breast cancer: Aussie research – Brinkwire

SYDNEY, April 28 (Xinhua) A new type of specialized immune cells that maintain the health of breast ducts has been discovered using advanced imaging techniques, pointing to better understanding and treatment of breast cancer, according to a latest Australian research.

The immune cells help to keep breast tissue healthy by regulating a vital process within mammary ducts the sites where milk is produced and transported, but also where most breast cancers arise, the Walter and Eliza Hall Institute of Medical Research said in a statement on Tuesday.

The researchers used high-resolution 3D imaging to observe how the cells monitor threats in the mammary ducts and help maintain tissue health.

We discovered an entirely new population of specialized immune cells, which we named ductal macrophages, squeezed in between two layers of the mammary duct wall, institute researcher Caleb Dawson said.

We were excited to find that these cells play an essential role at a pivotal point in mammary gland function called involution when lactation stops, milk-producing cells die and breast tissue needs to remodel back to its original state, he said.

We watched incredulously as the star-shaped ductal macrophages probed with their arms and ate away dying cells. The clearing action performed by ductal macrophages helps redundant milk-producing structures to collapse, allowing them to successfully return to a resting state.

When the researchers later removed the specialized cells from the mammary ducts they discovered that no other immune cells were able to swiftly carry out the essential process, according to the institute. The findings were published in scientific journal Nature Cell Biology.

More than 19,000 Australians are diagnosed with breast cancer every year and it is the most common cancer in Australian women, according to the institute.

The researchers, going forward, hope to explore the function of ductal macrophages at different stages of mammary gland development, such as the transitions into adulthood and pregnancy, Dawson said. Enditem

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Immune cell type in breast ducts points to better treatment of breast cancer: Aussie research - Brinkwire

Cell Biology

Assistant / Associate / Professor for School of Life Science and Technology job with SHANGHAITECH UNIVERSITY | 205309 – Times Higher Education (THE)

Officially established on September 30th 2013 by Chinas Ministry of Education, ShanghaiTech University is a small-scale research university of academic excellence jointly established by Shanghai Municipal Government and Chinese Academy of Sciences (CAS). ShanghaiTech focuses on science and engineering. The university consists of four schools and two research institutes: School of Physical Science and Technology (SPST), School of Information Science and Technology (SIST), School of Life Science and Technology (SLST), School of Entrepreneurship and Management (SEM), Shanghai Institute for Advanced Immunochemical Studies (SIAIS) and iHuman Institute.

Qualifications

SLST is seeking applications focused on, but not limited to, genomics and proteomics, epigenetics, RNA biology, systems and computational biology, stem cell biology and regenerative medicine, super-resolution microscopy, chemical biology and drug discovery, and translational medicine. Successful applicants should have an exceptional track record of research in life science or technology in the last five years. The recruited faculty members are expected to develop a first-rate research program and contribute to the educational missions of SLSTs undergraduate and graduate prog

Salary Package

Salary is highly competitive and commensurate with experience and academic accomplishments. ShanghaiTech also offers a comprehensive benefit package. On-campus professor apartment is provided.

ShanghaiTech will provide internationally competitive start-up funds, including support for Research Associates and Post-Doctoral fellows. Laboratory space will be provided to match research needs.

Application Procedure

Submit a cover letter (Firstname_Lastname_Cover_Letter.pdf), a 2-page research plan (Firstname_Lastname_Research_Plan.pdf), a CV (Firstname_Lastname_CV.pdf), up to 3 copies of most significant publications (Firstname_Lastname_Paper1-3.pdf), and the names of three references to SLST@shanghaitech.edu.cn.

Review of applications will start immediately and will continue until positions are filled.

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Assistant / Associate / Professor for School of Life Science and Technology job with SHANGHAITECH UNIVERSITY | 205309 - Times Higher Education (THE)

Cell Biology

Castle Biosciences Announces Publication of Validation Study for DecisionDx-SCC, Showing this Test is an Independent Predictor of Metastatic Risk in…

FRIENDSWOOD, Texas--(BUSINESS WIRE)-- Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, today announced the publication of development and validation data for DecisionDx-SCC, its prognostic test for patients diagnosed with high-risk cutaneous squamous cell carcinoma (SCC). The test is expected to be launched commercially in the second half of 2020.

The article titled, Validation of a 40-Gene Expression Profile Test to Predict Metastatic Risk in Localized High-Risk Cutaneous Squamous Cell Carcinoma, was published in the Journal of the American Academy of Dermatology (JAAD).

The study results demonstrate that DecisionDx-SCC is an independent predictor of metastatic risk that can complement current cancer risk-factor staging systems for patients with high-risk SCC.

As clinicians, we struggle with treatment decisions for patients with high-risk cutaneous squamous cell carcinoma due to the limitations of clinicopathologic based staging systems, said first author, Ashley Wysong, M.D., University of Nebraska Medical Center, Omaha NE. Validation of the DecisionDx-SCC test demonstrates significant progress in this area by integrating tumor-specific genetic information into clinical decision making. Having better prognostic information helps us to identify patients as low risk by tumor biology and manage them more conservatively with clinical surveillance, as well as provides us with data to help guide implementation of adjuvant interventions and clinical trial recommendations for those identified as high risk.

Disease and Study Background

Study Findings

DecisionDx-SCC is the second skin cancer test discovered, developed and validated by Castle Biosciences.

About Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers. Approximately 1 million patients are diagnosed with SCC each year in the U.S. While the majority of patients have a favorable prognosis, approximately 200,000 patients are identified as high risk. National guidelines provide for broad, aggressive treatment plan recommendations relative to low-risk patients. Traditional clinicopathologic based risk-factor staging systems suffer from low positive predictive value; meaning many more patients are classified as high risk than actually develop metastatic disease. This may lead to over- and under-treatment of a substantial number of cutaneous SCC patients. To address this clinical need, Castle Biosciences has developed a gene expression profile test designed to improve upon current staging systems and identify patients with cutaneous SCC at high risk for metastasis or recurrence, in order to enable more informed, objective clinical decisions regarding adjuvant therapy and other management options.

About Castle Biosciences

Castle Biosciences (Nasdaq: CSTL) is a commercial-stage dermatologic cancer company focused on providing physicians and their patients with personalized, clinically actionable genomic information to make more accurate treatment decisions. The Company currently offers tests for patients with cutaneous melanoma (DecisionDx-Melanoma, DecisionDx-CMSeq; http://www.SkinMelanoma.com) and uveal melanoma (DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq; http://www.MyUvealMelanoma.com), with products in development for other underserved cancers, the two most advanced of which are focused on patients with cutaneous squamous cell carcinoma, and patients who have a difficult-to-diagnose pigmented lesion. Castle Biosciences is based in Friendswood, Texas (Houston), and has laboratory operations in Phoenix, Arizona. For more information, visit http://www.CastleBiosciences.com.

DecisionDx-Melanoma, DecisionDx-CMSeq, DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq are trademarks of Castle Biosciences, Inc.

Forward-Looking Statements

The information in this press release contains forward-looking statements and information within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the safe harbor created by those sections. These forward-looking statements include, but are not limited to, statements concerning the ability of DecisionDx-SCC test results to appropriately direct cutaneous SCC patient work-up and treatment plans; the ability of DecisionDx-SCC to improve upon existing staging systems and accurately classify patient risk; and expectations of DecisionDx-SCC to enable de-escalation of care in patients identified as high risk by traditional staging and provide objective data to implement proper recommendations for actual high-risk patients. The words anticipates, believes, estimates, expects, intends, may, plans, projects, will, would and similar expressions are intended to identify forward-looking statements; although, not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions, or expectations disclosed in our forward-looking statements and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. These forward-looking statements involve risks and uncertainties that could cause our actual results to differ materially from those in the forward-looking statements, including, without limitation, the risks set forth in our Annual Report on Form 10-K for the year ended December 31, 2019, filed with the SEC on March 10, 2020, and in our other filings with the SEC. The forward-looking statements are applicable only as of the date on which they are made, and we do not assume any obligation to update any forward-looking statements, except as may be required by law.

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Cell Biology

Remote learning in the age of COVID-19 – Brandeis University

Faced with the challenge of maintaining high-quality education while teaching online, professors are adapting and innovating -- everything from take-home tests to sharing pictures of their teddy bears.

With most of higher education taking place online, professors all across the country are asking: How do you teach via Zoom?

It may involve leading a discussion with dozens of students, each in their own, separate video box with the likelihood they will end up talking over one another. Or conducting a science laboratory without a lab, or teaching musical performance with all the musicians at home.

And how do you provide the emotional support and sense of community many students crave right now?

As Brandeis faculty seek to maintain the highest quality education under extraordinary circumstances, they are improvising, innovating and pioneering new pedagogical methods.

They are sending students into Zoom breakout rooms to conduct small-group discussions; administering take-home and open-book exams; using online quizzes and Google Forms to test students' grasp of readings and lectures; and reaching out to students through one-on-one video conversations.

Some professors have tried to provide a sense of community by asking their students to send in pictures of their home workspaces, or foods they're cooking. Professor of psychology Ellen Wright cheered up her class by showing them a teddy bear wearing a face mask.

Brandeis has also revised its academic policy for the semester so students getting a C- or higher grade can take the class pass/fail.

"We are still in unchartered waters," said Alain Lempereur, the Alan B. Slifka Professor of Coexistence and Conflict at the Heller School for Social Policy and Management. "We need to reinvent a new way of connecting to each other."

Faculty strategies to enhance remote learning are big and small, serious and fun.

Devising -- and explaining -- a vaccine

For her advanced cell biology class, associate professor of biology Avital Rodal developed a new lecture on COVID-19. Since she knew the students were at home with family, she included some advice on communicating science to a lay audience.

On her take-home, open-book midterm, one question asked the students to describe the cell biological mechanism of action of one potential antiviral treatment for COVID-19 that seems particularly promising to you."

Answering the question required a deep-dive into the science behind coronavirus treatments, but Rodal added this challenge: "Write 1-2 sentences for nonscientists describing how this drug would work. Pick a specific person (a parent, a friend, a grandparent, a politician) and let me know who your audience is."

Sample answers included these:

"I would explain to my mother that the drug of interest prevents the early endosome, which is where the virus is originally housed inside the cell, from changing. By keeping the endosome in its immature state, the virus cannot take advantage of enzymes that an older endosome would have, and it would stay trapped, unable to infect the cell."

"If I were to explain the drug mechanism to my mom, then I would say that for a virus to spread among cells, it has to be cleaved by a protein scissor to fuse with the cellular material. Now, we have a drug that makes the protein scissor unable to function, so the virus will no longer be released into the cell, thus, slowing the infection rate."

Light-hearted whimsy

As part of her regular check-in with students, associate professor of psychology Ellen Wright asks how they are coping.

She set up a Google Form with questions like, Anything big going on that I should know about? Or just tell me something I don't already know about you and Is there anything I can do to help make life/things better for you?

Wright, who teaches a class on personality and another on sex differences, got a variety of answers. Some students said they felt happy to be with family or grateful that they werent sick. But others said they were feeling sad and a bit lonely.

One student asked Wright on the Google Form if she had a pet. Wright doesnt, but her husband used to own a toy store that sold teddy bears.

She dressed them up with the face masks she wears outside. "A little light-hearted whimsy lifted our spirits a bit," she said.

Getting outside

In her conservation biology class, associate professor of ecology Colleen Hitchcock normally has students document animal and plant species in Waltham as part of the Brandeis Bioliteracy Project.

This semester, the students identified flora and fauna near their homes, using iNaturalist, a popular nature app that helps users identify species and allows them to record their observations.

Hitchcock also invited alumni and other students to participate. Members of the Brandeis community reported seeing a North American porcupine, a frigatebird from the tropics, an American black bear footprint and, of course, lots of different squirrel species.

"Our project, which had been focused on documenting species in Waltham, has become one where students are sharing what they are seeing around the world," Hitchcock said. "It is really wonderful to see how students are embracing the healing power of nature to get outside and observe."

Mangia and managerial accounting

When she got the sense that the students in her Managerial Accounting class were missing campus life, Brenda Anderson decided community-building exercises were needed. She asked students to share photos of their home workspaces.

"I had about a 70% participation rate in a class of 50, and it was more than fabulous," said Anderson, a faculty member at both the Heller School for Social Policy and Management and the Brandeis International Business School. "Some were serious, some funny, and we had a few pets and home-cooked food items. Students loved it!"

The final slide read: "Now, as my wonderful, dear father in law used to say Mangia!!!"

To read about other faculty members experiences teaching remotely, visit Preparing for Teaching Continuity | Center for Teaching and Learning.

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Remote learning in the age of COVID-19 - Brandeis University

Cell Biology

UK Startup to Manufacture Cell and Gene Therapies with… – Labiotech.eu

The UK company MicrofluidX has closed a 1.6M (1.4 M) seed funding round to develop a microfluidic platform that could produce cell and gene therapies more cheaply than conventional cell cultures.

The funding round was led by UKI2S, a national seed investment fund targeting early-stage companies, as well as Longwall Ventures and Cambridge Angels.

MicrofluidX will use the funding to establish a prototype of its technology. With this prototype, the company then aims to compare the performance of its microfluidics approach to current cell culture techniques used to produce gene and cell therapies.

In the dynamic cell therapy space, one of the major bottlenecks facing the field is the manufacture and scaling process, as manual cell culturing techniques are often required. Applying microfluidic technology to the manufacturing process may be an answer to this issue.

Although it is less developed at the manufacturing level, microfluidics technology has long been part of research in cell biology. It has several advantages over conventional cell cultures. For example, it allows cell cultures to be controlled more precisely on chips, increases automation, and can reduce the consumption of expensive ingredients in the cell culture process by a factor of twenty.

According to MicrofluidX, its platform could scale up microfluidics far beyond just biology research. The aim is to run dozens of cell cultures in parallel, with the capacity to produce cells more cheaply and with a higher yield than with current manufacturing techniques.

The result is that we can leverage all the inherent advantages of microfluidic cell culture at a scale never seen before, MicrofluidXs founder and CEO, Antoine Espinet, told me. This leads to much lower bioprocessing costs, better control over the final product, and faster translation from research to commercialization.

In particular, the company is investigating its technologys capacity to produce immune T-cells a common type of cell used in immunotherapies such as CAR T-cell therapies and other cell types.

Whilst the regulatory agencies are now warming up to cell and gene therapies, there are still growing pains, especially around manufacturing, Pablo Lubroth, an investor with UKI2S, told me.

It is essential to not only support companies that produce the therapies themselves, but also companies that are developing enabling technologies to ensure these therapies can be effectively commercialized and therefore have a tangible benefit to the patient.

As well as manufacturing, microfluidics is gaining traction in diagnostics and screening. For example, another UK startup, Lightcast Discovery, was founded last year to screen cells using microfluidics and beams of light. Additionally, the Belgian nanofluidics company miDiagnostics last month raised 14M to commercialize its silicon chip diagnostics in collaboration with Johns Hopkins University in the US.

Image from Shutterstock

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UK Startup to Manufacture Cell and Gene Therapies with... - Labiotech.eu

Cell Biology

The Shadow of a Science Yet to Be Born – Discovery Institute

Here is a paper that should be in the files of everyone thinking about biological design. It is Peter Tompa and George Roses The Levinthal Paradox of the Interactome (2011), from the journalProtein Science. I have written about this paper before, but it needs much more attention from the ID community, or the scientific community at large, than it has yet received. Their argument is far more important than I can state in full detail here, but a couple of comments:

I have told hundreds (maybe thousands, now) of students and colleagues about this paper. Starting with basic facts about cell biology, Tompa and Rose explain that theparts of cells do not explain theoriginof cells. To understand the origin of cells, one must focus on thefunctional interrelationsof those parts, which relations occupy the very tiny space of alive in the incomprehensibly larger space of not alive. That is something Richard Dawkins too understands. As he wrote in The Blind Watchmaker (1987, p. 9, emphasis in original):

however many ways there may be of being alive, it is certain that there are vastly more ways of being dead, or rather not alive. You may throw cells together at random, over and over again for a billion years, and not once will you get a conglomeration that flies or swims or burrows or runs, or does anything, even badly, that could remotely be construed as working to keep itself alive.

Several years ago, when I first became convinced of the importance of this paper, Bill Dembski did me a favor and ran some calculations, using the formula (p. 2075) for the possible pairwise interactions of the protein parts of a bacterial cell. Bills calculations are here. You can see that he stopped at 100 proteins. As I recall, what Bill said to me (with a laugh) was I think this is enough to make the point, Paul.

Any relation or interaction within a cell is not a material object. It is not a part or a thing. The relations that matter to the living state arefunctions, and, while requiring material parts, the functions cannot be reduced to those parts. Relations are inherently higher-level properties. Tompa and Rose argue that the space of possible interrelations that fail to yield the living state is so much larger than the tiny neighborhood of alive that, if the living state is disrupted, the parts of the cell will never find their way back to that state. Instead they embark on a one-way or irreversible random walk out into the universe of not-alive. This is why a bacterium whose membrane or cell wall is disrupted by sonication in a sterile buffer will never come back to life even though, at that moment, all the molecular parts (DNA, RNA, ribosomes, proteins, lipids, etc.) are co-present in the same microenvironment.

The essential relations have been lost, irretrievably. The living state,a system of relations, presupposes material things. It is not, however, a material thing itself, and cannot be reduced to materiality. Thus, the bottom-up approach to the origin of life cannot possibly succeed, because it is committed to a category error (i.e., error = the parts of a system are causally primary). Category errors do not yield to further effort.

So, what I say to students is that Tompa and Rose 2011 represents the shadow of a science yet to be born, a science of biological design. The image you should have is the shadow of someone, standing outside a window, with the bright sun at his back. His shadow falls through the window into the room where we are sitting, and we can trace its outline. This unborn science will explain why attempting to construct the living state bottom-up, from its parts, is doomed to failure as quixotic an enterprise as trying to build a perpetual motion machine. The paper by Tompa and Rose casts a shadow for us, and we need to trace its outline and derive the theory behind the shadow.

Note carefully: Tompa and Rose do not themselves support a design view of the origin of life. They argue that some unknown, incremental pathway assembled cells: Presumably, earlyearth life forms originated through an accumulation of changes of ever increasing complexity (p. 2077). But their interactome analysis does not explain how that pathway would have been traversed, without design only that (as noted above) having the parts on hand will not yield a cell.

A Theory Worthy of Trust

Einstein, in a famous 1918 letter to his friend Michele Besso, put the general epistemological point this way (quoted by Gerald Holton, emphasis added):

a theory which wishes to deserve trustmust be built upon generalizable facts.Old examples: Chief postulates of thermodynamics [based] on impossibility of perpetuum mobile. Mechanics [based] on grasped [ertasteten]law of inertia. Kinetic gas theory [based] on equivalence of heat andmechanical energy (also historically). Special Relativity on the constancy of light velocity and Maxwells equation for the vacuum, whichin turn rest on empirical foundations. Relativity with respect to uniform[?] translation is a fact of experience.General [Relativity]: Equivalence of inertial and gravitational mass.Neverhas a truly useful and deep-going theory really been found purely speculatively.

A new book by Change Tan and Rob Stadler,The Stairway to Life: An Origin-of-Life Reality Check(2020), is also helpful in this regard.

Photo credit:Adeline Ferolo on Unsplash.

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The Shadow of a Science Yet to Be Born - Discovery Institute

Cell Biology

The Drug Discoverer – Book published in tribute to the late Dr Susan Lindquist HSF1 and Molecular Chaperones in Biology and Cancer – The – The…

Image: Dr Susan Lindquist. Source: Wikimedia, CC BY-SA 3.0.

Like so many, I was shocked and saddened to hear of the untimely death from cancer on October 27, 2016, of Dr Susan Lindquist.

Sue was a true scientific pioneer and innovator, specialising in the field of protein foldingand its role in cancer and neurodegenerative diseases. She was also a great advocate for women in STEM.

Her cutting edge research and radical ideas were not only trailblazing but often viewed as controversial at the time and met with initial disbelief.

Sues impact on both basic and translational research was immense. Of particular relevance to my own research and that of The Institute of Cancer Research, London, was her work on the molecular chaperone HSP90 (Heat Shock Protein 90), another heat shock protein and chaperone HSP70 and the transcription factor HSF1 (Heat Shock Factor 1).

An ebook dedicated to the life and work of Sue Lindquist, edited by Marc Mendillo, David Pincus and Ruth Scherz-Shouval, has just been published with the title HSF1 and Molecular Chaperones in Biology and Cancer.

This project was initiated at a meeting in Sue's honour in Madridthat I co-organized with Nabil Djouder, Wilhelm Krek and Xiaohong Helena Yang.

Individual chapters are listed in PubMed as articles published in Advances in Experimental Medicine and Biology.

I was honoured to contribute the closing chapter of the monograph, writing what was very much a personal reflection on the translational aspects of the field of molecular chaperones and the discovery and development of inhibitors of HSP90, HSP70 and HSF1.

Sue spent the initial part of her career at the University of Chicagoand then later was at the Whitehead Institute in Boston, where she was also Professor of Biology at the Massachusetts Institute of Technology (MIT), and latterly also an associate member of the Broad Institute of MITand Harvard University.

Earlier, Sue earned an undergraduate degree in microbiology from University of Illinois at Urbana-Champaignand a PhD in biology from Harvard.

Sues research into the biological function of HSP90 provided valuable background to our own research to discover small-molecule inhibitors of chaperones, culminating in the discovery in the Cancer Research UK Cancer Therapeutics Unit at the ICR, in collaboration with UK biotech company Vernalis, of the clinical candidate luminespib also previously known as VER52296 and AUY922 which was licensed to Novartisand has shown clinical activity in breastand non small cell lung cancer.

This therapeutic activity is based on the role of HSP90 in chaperoning or stabilising many cancer-causing proteins for example the product of the HER2 gene which is amplified and drives the growth of many breast (and other) cancers and the product of mutated forms of the ALK and EGFR genes that drive many non small cell lung cancers.

Inhibition of HSP90 blocks its ability to chaperone and stabilise HER2 and mutant EGFR and ALK, leading to their destruction by the cells waste disposal system for proteins, known as the proteasome.

At least 17 small-molecule HSP90 inhibitors have entered clinical trials. However, to date none have been approved. This may be because we have not as yet found the way to use these drugs most optimally especially in combination with other agents.

In leading one of the teams that championed HSP90 as a drug target, I was impressed by HSP90s ability to chaperone many different proteins that contribute to cancers growth and spread.

And we reasoned that by inhibiting the function of HSP90 we would be able to eliminate multiple cancer-causing proteins and therefore not only to block cancer growth but also to reduce its ability to adapt and evolve to become resistant to treatment.

This thinking was an extension into the oncology domain of Sues pioneering and at times controversial research demonstrating that HSP90 could act as a kind ofgenetic capacitor in phenotypic variation and so-called morphological evolution initially buffering hidden genetic variants before releasing, under conditions of environmental stress, potentially useful forms for selection in evolutionary bursts.

In addition to HSP90, we and others have also designed and synthesized inhibitors of heat shock proteins and chaperones in HSP70 family. HSP70 family members have also been validated as drug targets. HSP70 proteins are, however, technically much tougher to drug.

Prior to her work on HSP90, Sue had been involved in the very early work to understand how elevated temperatures trigger the 'heat shock response' mediated by HSF1 leading to the production of heat shock proteins, many of which are chaperones like HSP90.

Sue also carried out crucial early work to understand the features of HSP90 that allow it to chaperone both kinases and also transcription factors such as the glucocorticoid receptor.

Furthermore, in later years Sues lab contributed hugely to understanding the important role of HSF1 in cancerand provided important validation that helped underpin our subsequent discovery of small-molecule inhibitors of the HSF1 pathway.

Among her many awards and accolades, Sue was in 2015 elected as a Foreign Member of the UKs Royal Society for which her biographyreads:

Susan Lindquist has transformed our understanding of how protein folding shapes biological systems. She has made groundbreaking contributions in genetics, cell biology and biochemistry, using organisms as diverse as fungi, fruit flies, mustard plants and mammals.

She discovered the functions of heat-shock proteins, identified prions as conduits of protein-based inheritance, and pioneered new platforms for neurodegenerative disease. She established the key role of the heat-shock proteins in tumour progression and the evolution of fungal drug resistance. She discovered that protein-folding buffers and releases genetic variation in response to environmental stress, providing the first plausible explanation for rapid bursts of evolution.

This an astonishing list of achievements.

In addition to the application of her discoveries to cancer, Sues pioneering work on the inheritance of proteins with new, self-perpetuating shapes, as distinct from new DNA sequences, has great relevance to understanding and potentially treating neurological illnesses such as Alzheimer's, Parkinson's, Huntington's and CreutzfeldtJakob disease.

Overall, Sue Lindquists research has made an enormous contribution to our understanding of protein folding in health and disease.

At the end of my articlein the monograph dedicated to her life in science, I express the profound hope that our clinical candidate inhibitor of the HSF1 pathway which is showing promising activity in models of ovarian cancer will make a real difference to the treatment of this disease which cruelly took Sue away from us far too early.

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Cell Biology

The Future Of Manufacturing Is Built With Biology. Or, How This Biotech Startup Is Challenging The Trillion-Dollar Global Chemical Industry. – Forbes

EnginZyme's technology could dramatically reduce the equipment and energy costs of manufacturing by ... [+] harnessing nature's ability to make chemicals, potentially transforming the trillion-dollar global chemistry market.

Manufacturing is a crude science. We destroy mountains to extract heavy metals, which we then cook at high pressures and temperatures to make things like plastic, nylon, and rubber. Compare this to nature: Living cells and organisms can make all the chemicals needed to thrive across a wide range of environments, often requiring little more than carbon atoms and some sunlight.

Nature apparently has a much better solution, says EnginZyme CEO Karim Engelmark Cassimjee. His company sees harnessing biology as a manufacturing platform not as a mere sustainability play, but as a trillion-dollar global market opportunity.

On Wednesday, April 22, EnginZyme announced that they raised 6.4 million in a Series A round led by Sofinnova Partners, bringing the companys total funding to over 10 million. A spin-out of the Arrhenius Laboratory at Stockholm University, the six-year-old company has been quietly working on a new technology that is set to revolutionize the impact that synthetic biology has on the manufacturing of everything from food ingredients to biomaterials to active pharmaceutical ingredients.

Broadly speaking, companies are starting to adopt biomanufacturing as their preferred method of production. After all, whats good for the environment is generally good for business (less energy, fewer resources, less chemical processing, and lower costs). Biomanufacturing represents a growing share of the products we use every day. As an example, high-performance bio-electronics will probably end up in your next smartphone, laptop, watch, or television not because their made with biology, but simply because they work better.

But what is astonishing about EnginZymes approach is this: It is all done all through the use of cell-free synthetic biology, a technique that can harness the power to build with biology, without needing the cell itselfand all of the complexity that goes along with it.

Our platform mimics fermentation, says Cassimjee, talking about the age-old process of using biology to make everything from kimchee to beer. Fermentation has been a cornerstone of the biotech industry for decades now. But EnginZymes technology promises a 40% reduction in CapEx (the cost of manufacturing equipment and maintenance) and a 70% reduction in energy.

We use biology and enzyme catalysts instead of metal catalysts, at lower temp and pressure, says Cassimjee. This is a game-changer that could enable EnginZyme to compete with the slower moving giants of the chemical industry, allowing for smaller-scale, on-demand manufacturingsomething this post-COVID world and its need for localized supply chains is clamoring for.

Cassimjee wants to take on nothing less than the entire chemical industry, everything from plastics to bulk chemicals. But the task wont necessarily be easy for a startup. For each application, we have to produce a chemical process and production plant, he says. And the end game is coming up with a proven, large-scale production strategy for making whatever it is the world needs from chemistry.

The fixed-bed technology EnginZymes is using is already well understood, and its separation technology is also well understood. EnginZymes secret saucethe advancement that has the potential to change the paradigm of bio-based manufacturingis a special material that can bind to enzymes while allowing them to maintain their functionality.

With conventional chemistry, You put everything in the tank and mix, says Cassimjee. That chemistry depends on enzymes, the proteins that cause a chemical reaction to move forward. For example, when we hear about a company that has engineered a bacterium to turn sugar into a high-value chemical, it is actually a set of enzymes inside the bacteria that does the hard work of transforming sugar into a chemical. The bacteria simply act as tiny tanks that produce and mix the enzymes, facilitating the fermentation process that makes useful chemical for us.

But with this new tech, the biological enzymes are fixed, and the various ingredients flow through the fixed enzymes, and the final product flows out the other end.

As Ive written before, synthetic biology and the protein design world are now able to engineer enzymes for all sorts of novel applications. And because enzymes are long chains of 20 different amino acids, the array of different possible enzymes available is more than the number of stars in the universe, giving humans working from first-order design principles an infinite design space to work within.

If a company has a specific molecule in mind, we can help them make it, Cassimjee says.

EnginZyme works with companies who are using biocatalystsenzymes made with biologyto scale their processes up to industrial production scales.

By separating out the enzymes from the bacteria, EnginZyme greatly simplifies the chemical production process. It significantly simplifies the process, removing the extraneous chemical reactions and energy necessary to keep the bacteria alive. Instead of using a large vat of bacteria that is expensive to set up and run, companies can use an efficient column filled with concentrated enzymes, continuously feeding sugar in the top, and getting their product out the bottom.

As Cassimjee describes it, Its like comparing somebody hand-building a car to Henry Ford and the automated assembly line.

Stevia is a naturally sweet substitute for sugar, but can synthetic biology make it less bitter?

One example of how EnginZymes technology will impact us is in the world of nutrition. The sugar we add to our cakes, cookies and sauces is homogenous, meaning that every molecule (sucrose) is the same. But this isnt natural, and it certainly isnt healthy. I have written before about companies that are developing healthy alternatives to sugar, like Codexis with Stevia. EnginZymes technology could enable a future where we have access to many different types of healthy sugars and sugar replacements, each one suited for a different specific use case.

We can see the same thing happening with plastics, or with other molecules. We currently have different plastic molecules that are used for different purposes (plastic bottles versus plastic bags, for example), but in the future we could develop greener alternatives to all of these, producing them from waste or making them biodegradable.

Many in the startup world would tell you that venture funding is nearly frozen right now, as funds are evaluating which businesses will be able to survive the new world we live in. With that in mind, for EnginZyme to raise such an impressive round of funding, somebody must believe they are onto something truly transformative.

Biomanufacturing isnt just about making our current materials cheaper. It is also about bringing incredible new products to market that outperform the best products that conventional chemistry can give us now. By learning from and building upon the diversity that nature has given us, we can make a better product in a better way.

Follow me on twitter at @johncumbers and @synbiobeta. Subscribe to my weekly newsletters in synthetic biology.

Thank you to Calvin Schmidt for additional research and reporting in this article. Im the founder ofSynBioBeta, and some of the companies that I write aboutincluding Codexisare sponsors of theSynBioBeta conferenceandweekly digestheres the full list of SynBioBeta sponsors.

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The Future Of Manufacturing Is Built With Biology. Or, How This Biotech Startup Is Challenging The Trillion-Dollar Global Chemical Industry. - Forbes

Cell Biology

This is how human cells respond to stress – Devdiscourse

Scientists in a new study observed and studied the response of human cells on coming in contact with stress. Cells are often exposed to stressful conditions that can be life-threatening, such as high temperatures or toxins. Fortunately, human cells are masters of stress management with a powerful response program: they cease to grow, produce stress-protective factors, and form large structures, which are called stress granules.

Scientists at the Biotechnology Center (BIOTEC) of the TU Dresden and the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), together with partners in Heidelberg and St. Louis (USA) have investigated how these mysterious structures assemble and dissolve, and what may cause their transition into a pathological state as observed in neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis). The results of the study have been published in the journal - Cell.

ALS is a hitherto incurable disease of the central nervous system in which the motor neurons - nerve cells responsible for the muscles movement - gradually die. Stress granules are formed in the cytoplasm of the cell and assemble from a large number of macromolecular components such as messenger RNAs and RNA-binding proteins.

Stress granules usually disassemble when the stress subsides, a process that is promoted by the dynamic nature of stress granules. However, a hallmark of ALS is the presence of non-dynamic, persistent forms of stress granules. "In ALS, patients suffer from muscle weakness and paralysis. Stress granule-containing motor neurons slowly degenerate, causing a progressive loss of motor functions," said Dr. Titus Franzmann, one of the senior authors of the publication.

"We need to better understand the complex biology of stress granules in order to design and develop future therapeutic strategies that counteract the course of the disease. But the complex environment of the cells within an organism makes this difficult," added Franzmann. In order to systematically test their hypotheses about the assembly of stress granules and the pathology causing molecular changes, the scientists developed a controlled environment using an in vitro system with purified components that allowed the recreation of stress granules in a test tube.

They observed stress granule assembly step by step and characterized the critical factors underlying their dynamics. "Stress granules have a very complex structure. Nevertheless, their formation depends primarily on the behavior of a single protein - the RNA-binding protein G3BP. This protein undergoes a critical structural change: Under non-stress conditions, G3BP adopts a compact state that does not allow stress granules to assemble," said Dr Jordina Guillen-Boixet, one of the first authors of the study.

"But under stress, RNA molecules bind to G3BP allowing multiple interactions that promote the assembly of dynamic stress granules. The subsequent transition from dynamic into non-dynamic state, which may be caused for example by prolonged stress, may trigger the death of the motor neurons, as we can observe in the disease ALS," added Guillen-Boixet. The research project was initiated in 2015 and led by the Alberti research group at TU Dresden's BIOTEC.

The close co-operation of 23 scientists from the TU Dresden, the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, the European Molecular Biology Laboratory in Heidelberg and the Washington University in St. Louis (USA) was central for the success of the project. "There is a number of remaining questions. Our experimental system at BIOTEC is now available for further testing and will be central to developing new diagnostics and therapeutics to combat neurodegenerative diseases such as ALS," said Prof. Simon Alberti. (ANI)

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This is how human cells respond to stress - Devdiscourse

Cell Biology

Eleven Princeton faculty elected to American Academy of Arts and Sciences – Princeton University

Princeton faculty members Rubn Gallo, M. Zahid Hasan, Amaney Jamal, Ruby Lee, Margaret Martonosi, Tom Muir, Eve Ostriker, Alexander Smits, Leeat Yariv and Muhammad Qasim Zaman have been named members of the American Academy of Arts and Sciences. Visiting faculty member Alondra Nelson also was elected to the academy.

They are among 276 scholars, scientists, artists and leaders in the public, nonprofit and private sectors elected this year in recognition of their contributions to their respective fields.

Gallo is the Walter S. Carpenter, Jr., Professor in Language, Literature, and Civilization of Spain and a professor of Spanish and Portuguese. He joined the Princeton faculty in 2002. His most recent book is Conversacin en Princeton(2017)with Mario Vargas Llosa, who was teaching at Princeton when he received the Nobel Prize in Literature in 2010.

Gallos other books include Prousts LatinAmericans(2014);Freuds Mexico: Into the Wilds of Psychoanalysis(2010); Mexican Modernity: the Avant-Garde and the Technological Revolution(2005); New Tendencies in Mexican Art(2004); andThe Mexico City Reader(2004). He is currently working on Cuba: A New Era, a book about the changes in Cuban culture after the diplomatic thaw with the United States.

Gallo received the Gradiva award for the best book on a psychoanalytic theme and the Modern Language Associations Katherine Singer Kovacs Prize for the best book on a Latin American topic. He is a member of the board of the Sigmund Freud Museum in Vienna, where he also serves as research director.

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Nick Barberio, Office of Communications

Hasan is the Eugene Higgins Professor of Physics. He studiesfundamental quantum effects in exotic superconductors, topological insulators and quantum magnetsto make new discoveries about the nature of matter, work that may have future applications in areas such asquantum computing. He joined the faculty in 2002and has since led his research team to publish many influential findings.

Last year, Hasans lab led research that discovered that certain classes of crystals with an asymmetry like biological handedness, known as chiral crystals, may harbor electrons that behave in unexpected ways. In 2015, he led a research team that first observed Weyl fermions, which, if applied to next-generation electronics, could allow for a nearly free and efficient flow of electricity in electronics, and thus greater power, especially for computers.

In 2013, Hasan was named a fellow of the American Physical Society for the experimental discovery of three-dimensional topological insulators a new kind of quantum matter. In 2009, he received a Sloan Research Fellowship for groundbreaking research.

Photo by Tori Repp/Fotobuddy

Jamal is the Edwards S. Sanford Professor of Politics and director of the Mamdouha S. Bobst Center for Peace and Justice. She has taught at Princeton since 2003. Her current research focuses on the drivers of political behavior in the Arab world, Muslim immigration to the U.S. and Europe, and the effect of inequality and poverty on political outcomes.

Jamal also directs the Workshop on Arab Political Development and the Bobst-AUB Collaborative Initiative. She is also principal investigator for the Arab Barometer project, which measures public opinion in the Arab world. She is the former President of the Association of Middle East Womens Studies.

Her books include Barriers to Democracy (2007), which won the 2008 APSA Best Book Award in comparative democratization, and Of Empires and Citizens, which was published by Princeton University Press (2012). She is co-editor of Race and Arab Americans Before and After 9/11: From Invisible Citizens to Visible Subjects (2007) and Citizenship and Crisis: Arab Detroit after 9/11 (2009).

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Lee is the Forrest G. Hamrick Professor in Engineering and professor of electrical engineering. She is an associated faculty member in computer science. Lee joined the Princeton faculty in 1998.Her work at Princeton explores how the security and performance of computing systems can be significantly and simultaneously improved by hardware architecture. Her designs of secure processor architectures have strongly influenced industry security offerings and also inspired new generations of academic researchers in hardware security, side-channel attacks and defenses, secure processors and caches, and enhanced cloud computing and smartphone security.

Her research lies at the intersection of computer architecture, cybersecurity and, more recently, the branch of artificial intelligence known as deep learning.

Lee spent 17 years designing computers at Hewlett-Packard, and was a chief architect there before coming to Princeton. Among many achievements, Lee is known in the computer industry for her design of the HP Precision Architecture (HPPA or PA-RISC) that powered HPs commercial and technical computer product families for several decades, and was widely regarded as introducing key forward-looking features. In the '90s she spearheaded the development of microprocessor instructions for accelerating multimedia, which enabled video and audio streaming, leading to ubiquitous digital media.Lee is a fellow into the Association for Computing Machinery and the Institute of Electrical and Electronics Engineers.

Margaret Martonosi, the Hugh Trumbull Adams 35 Professor of Computer Science, specializes in computer architecture and mobile computing with an emphasis on power efficiency. She was one of the architects of the Wattch power modeling infrastructure, a tool that was among the first to allow computer scientists to incorporate power consumption into early-stage computer systems design. Her work helped demonstrate that power needs can help dictate the design of computing systems. More recently, Martonosis work has also focused on architecture and compiler issues in quantum computing.

She currently serves as head of the National Science Foundations Directorate for Computer and Information Science and Engineering, one of seven top-level divisions within the NSF. From 2017 until February 2020, she directed Princetons Keller Center for Innovation in Engineering Education, a center focused on enabling students across the University to realize their aspirations for addressing societal problems. She is an inventor who holds seven U.S. patents and has co-authored two technical reference books on power-aware computer architecture. In 2018, she was one of 13 co-authors of a National Academies consensus study report on progress and challenges in quantum computing.

Martonosi is a fellow of the Association for Computing Machinery (ACM) and the Institute of Electrical and Electronics Engineers IEEE). Among other honors, she has received a Jefferson Science Fellowship, the IEEE Technical Achievement Award, and the ACM SIGARCH Alan D. Berenbaum Distinguished Service Award. She joined the Princeton faculty in 1994.

Muir is the Van Zandt Williams, Jr. Class of 65 Professor of Chemistry and chair of the chemistry department. He joined Princeton in 2011 and is also an associated faculty member in molecular biology.

He leads research in investigating the physiochemical basis of protein function in complex systems of biomedical interest. By combining tools of organic chemistry, biochemistry, biophysics and cell biology, his lab has developed a suite of new technologies that provide fundamental insight into how proteins work. The chemistry-driven approaches pioneered by Muirs lab are now widely used by chemical biologists around the world.

Muir has published over 150 scientific articles and has won a number of honors for his research.He received a MERIT Award from the National Institutes of Health and is a fellow of American Association for the Advancement of Science and the Royal Society of Edinburgh.

Nelson is the Harold F. Linder Chair in the School of Social Science at the Institute for Advanced Study and a visiting lecturer with the rank of professor in sociology at Princeton. She is president of the Social Science Research Council and is one of the country's foremost thinkers in the fields of science, technology, social inequalityand race. Her groundbreaking books include "The Social Life of DNA: Race, Reparations, and Reconciliation after the Genome" (2016) and "Body and Soul: The Black Panther Party and the Fight Against Medical Discrimination" (2011).Her other books include"Genetics and the Unsettled Past: The Collision of DNA, Race, and History" (with Keith Wailoo of Princeton and Catherine Lee) and"Technicolor: Race, Technology, and Everyday Life" (with Thuy Linh Tu). In 2002 she edited "Afrofuturism," a special issue of Social Text.

Nelson's writings and commentary also have reached the broader public through a variety of outlets. She has contributed to national policy discussions on inequality and the implications of new technology on society.

She is an elected fellow of the American Academy of Political and Social Science, the Hastings Centerand the Sociological Research Association. She serves on several advisory boards, including the Andrew. W. Mellon Foundation and the American Association for the Advancement of Science.

Ostriker, professor of astrophysical sciences, studies the universe. Her research is in the area of theoretical and computational astrophysics, and the tools she uses are powerful supercomputers and algorithms capable of simulating the birth, life, death and reincarnation of stars in their galactic homes. Ostriker and her fellow researchers build computer models using fundamental physical laws ones that govern gravity, fluid dynamics and electromagnetic radiation to follow the evolution of conditions found in deep space.

Ostriker, who came to Princeton in 2012, and her team have explored the formation of superbubbles, giant fronts of hot gas that billow out from a cluster of supernova explosions. More recently, she and her colleagues turned their focus toward interstellar clouds.

The research team uses computing resources through the Princeton Institute for Computational Science and Engineering and its TIGER and Perseus research computing clusters, as well as supercomputers administered through NASA. In 2017, Ostriker received a Simons Investigator Award.

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Nick Donnoli, Office of Communications

Smits is the Eugene Higgins Professor of Mechanical and Aerospace Engineering, Emeritus. His research spans the field of fluid mechanics, including fundamental turbulence, supersonic and hypersonic flows, bio-inspired flows, sports aerodynamics, and novel energy-harvesting concepts.

He joined the Princeton faculty in 1981 and transferred to emeritus status in 2018. Smits served as chair of the Department of Mechanical and Aerospace Engineering for 13 years and was director of the Gas Dynamics Laboratory on the Forrestal Campus for 33 years. During that time, he received several teaching awards, including the Presidents Award for Distinguished Teaching.

Smits has written more than 240 articles and three books, and edited seven volumes. He was awarded seven patents and helped found three companies. He is a member of the National Academy of Engineering and a fellow of the American Physical Society, the American Institute of Aeronautics and Astronautics, the American Society of Mechanical Engineers, the American Association for the Advancement of Science, and the Australasian Fluid Mechanics Society.

Yariv is the Uwe Reinhardt Professor of Economics. An expert in applied theory and experimental economics, her research interests concentrate on game theory, political economy, psychology and economics. She joined the faculty in 2018. Yariv also is director of the Princeton Experimental Laboratory for the Social Sciences.

She is a member of several professional organizations and is lead editor of American Economic Journal: Microeconomics, a research associate with the Political Economy Program of the National Bureau of Economic Research, and a research fellow with the Industrial Organization Programme of the Centre for Economic Policy Research.

She is also a fellow of the Econometric Society and the Society for the Advancement of Economic Theory, and has received numerous grants for researchand awards for her many publications.

Zaman, who joined the Princeton faculty in 2006, is the Robert H. Niehaus 77 Professor of Near Eastern Studies and Religion and chair of the Department of Near Eastern Studies.

He has written on the relationship between religious and political institutions in medieval and modern Islam, on social and legal thought in the modern Muslim world, on institutions and traditions of learning in Islam, and on the flow of ideas between South Asia and the Arab Middle East. He is the author of Religion and Politics under the Early Abbasids (1997), The Ulama in Contemporary Islam: Custodians of Change (2002), Ashraf Ali Thanawi: Islam in Modern South Asia (2008), Modern Islamic Thought in a Radical Age: Religious Authority and Internal Criticism (2012), and Islam in Pakistan: A History (2018). With Robert W. Hefner, he is also the co-editor of Schooling Islam: The Culture and Politics of Modern Muslim Education (2007); with Roxanne L. Euben, of Princeton Readings in Islamist Thought (2009); and, as associate editor, with Gerhard Bowering et al., of the Princeton Encyclopedia of Islamic Political Thought (2013). Among his current projects is a book on South Asia and the wider Muslim world in the 18th and 19th centuries.

In 2017, Zaman received Princetons Graduate Mentoring Award. In 2009, he received a Guggenheim Fellowship.

The mission of the academy: Founded in 1780, the American Academy of Arts and Sciences honors excellence and convenes leaders from every field of human endeavor to examine new ideas, address issues of importance to the nation and the world, and work together to cultivate every art and science which may tend to advance the interest, honor, dignity, and happiness of a free, independent, and virtuous people.

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Eleven Princeton faculty elected to American Academy of Arts and Sciences - Princeton University