Category Archives: Cell Biology

Science journalist Rebecca Skloot to speak on ‘The Immortal Life of … – Virginia Tech Daily

She was born Loretta Pleasant. For most of her life, she was known as Henrietta Lacks. Since the 1950s, generations of cell biologists have known her mostly without being aware of it as HeLa, the nickname for the line of cells that inaugurated a new era in medical research.

The medical odyssey that made Lacks cells a cornerstone of modern medicine, chronicled in Rebecca Skloots 2010 bestseller "The Immortal Life of Henrietta Lacks," is a stunning object lesson in informed consent and bioethics and a sobering chapter in the long, shameful history of racial inequity and exploitation in medicine.

On April 11, Skloot, along with Shirley Lacks and Jeri Lacks Whye, will tell Lacks story and explore the troubling historical and ethical questions woven through it in a lecture on Virginia Techs Blacksburg campus.

The talk, part of the Hugh and Ethel Kelly Lecture Series, will take place at 2 p.m. in the Haymarket Theatre at Squires Student Center. Hosted by the Institute for Critical Technology and Applied Science in partnership with the College of Engineering, the event is free and open to the public but registration is requested.

The series of events that put Lacks at the center of a revolution in medical research began in 1951, when the Black mother of five sought treatment at Johns Hopkins Hospital for what turned out to be an aggressive cervical cancer. During the course of her treatment, doctors collected cells from her tumor and passed them along to a Johns Hopkins researcher wrestling with the challenge then consuming the medical community: growing human cells outside the human body.

Lab-grown cells would allow researchers to perform experiments and test treatments without endangering human patients. But until the cells from Lacks tumor showed up, no sample had ever survived for longer than a few days.

Lacks cells were different. They doubled their population every 24 hours in an apparently inexhaustible supply of identical copies. Lacks died in August 1951, but her cells which she didnt know were being cultured and hadnt given researchers consent to use divided over and over again in the laboratory, becoming the first immortalized human cell line.

This unlimited supply of cells transformed medical research. The vaccine for polio was developed through experiments conducted on HeLa cells. Researchers have relied on them to study diseases, including measles mumps, HIV, and ebola, and to develop treatments for cancers and viruses. HeLa cells were the first to be cloned and the first to be sent to space. They provided the backdrop for fundamental discoveries in genetics and other aspects of cell biology.

All of this was done without consulting, or even informing, Lacks' family, who only became aware that the cell line existed in the 1970s when they began receiving requests from researchers for blood samples. As part of the massive scientific and profit-making enterprise that was by then operating around HeLa cells, members of the family were used in research again, without their consent and their medical records shared.

It wasnt until Skloot began the reporting that ultimately became "The Immortal Life of Henrietta Lacks" that the Lacks family became aware of the magnitude of Henriettas transformative contributions to medicine and the lucrative biotech enterprise that fueled this research bonanza. Lacks' biological material had allowed companies to rake in massive profits selling HeLa cells by the trillions, but her descendants who shared the same biological material hadn't received any of that windfall.

Skloot used some of the books proceeds to establish The Henrietta Lacks Foundation, which has helped support some of the familys expenses. Some biotech companies have since contributed to this fund. But the ongoing debate over the responsible approach to Lacks legacy highlights the necessity of continuing to wrestle with these issues.

Sloots work, which covers topics from food politics to the intersection of race and medicine, has been featured in The New York Times and on National Public Radio, CBS Sunday Morning, the podcast "Radiolab," and numerous other outlets.

She has been recognized with awards from organizations including the National Academies of Science, the American Association for the Advancement of Science, and the Wellcome Trust.

She holds a bachelors degree in biological science and a masters degree in creative nonfiction.

The Hugh and Ethel Kelly Lecture Series is made possible by a fund from the estate of Ethel Kelly, who generously supported Virginia Tech and the College of Engineering in honor of her husband, Hugh. Hugh Kelly earned bachelors and masters degrees from the university and went on to play key roles in multiple groundbreaking projects over a long career at Bell Laboratories.

To honor Hugh Kellys technical accomplishments and the couples support of Virginia Tech, the College of Engineering and the Institute for Critical Technology and Applied Science established the lecture series and renamed the institute's headquarters building Kelly Hall in 2013. The Kellys generosity has allowed the institute to bring Nobel laureates, Pulitzer Prize winners, and other visionary leaders and thinkers to Blacksburg to share their work with the Virginia Tech community.

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Science journalist Rebecca Skloot to speak on 'The Immortal Life of ... - Virginia Tech Daily

How cell mechanics influences everything | MIT News … – MIT News

High in the treetops of a Chinese rainforest, Ming Guo began to explore the influence of a single cell.

A student in Chinas Tsinghua University, Guo was studying the mechanical properties of plant cells. As part of his masters thesis he took on an intriguing question: Does a cells physical integrity its size, shape, squishiness, or stiffness have anything to do with how tall a tree grows?

In search of an answer, Guo visited forests across the Yunnan province, collecting leaves from the tallest trees, some towering over 200 feet too high for Guo himself to climb. So, he enlisted the help of a student in the universitys rock climbing club, who scaled the trees and retrieved leaves at various heights along their length.

After analyzing the individual plant cells within each leaf, Guo observed a pattern: The higher the leaves, the smaller the cells. And, more interesting still, the size of a single cell could more or less predict how tall a tree can grow.

This early work in tree cells made one thing clear in Guos mind: A cells physical form can play a role in the development of an entire organism. This realization motivated him to study cell mechanics, in plant and eventually animal cells, to see what more a cells physical properties can reveal about how cells, tissues, organs, and whole organisms grow.

People study cells in the context of their biology and biochemistry, but cells are also simply physical objects you can touch and feel, Guo says. Just like when we construct a house, we use different materials to have different properties. A similar rule must apply to cells when forming tissues and organs. But really, not much is known about this process.

His work in cell mechanics led him to MIT, where he recently received tenure and is the Class of 54 Career Development Associate Professor in the Department of Mechanical Engineering.

At MIT, Guo and his students are developing tools to carefully poke and prod cells, and observe how their physical form influences the growth of a tissue, organism, or disease such as cancer. His research bridges multiple fields, including cell biology, physics, and mechanical engineering, and he is working to apply the insights from cell mechanics to engineer materials for biomedical applications, such as therapies to halt the growth and spread of diseased and cancerous cells.

MIT is a perfect place for that in the long run, Guo says. Its cross-disciplinary and always very inspiring, and by interacting with different people outside of the field, you get more ideas. Its more likely that you can dig up something useful.

The nature of physical objects

Guo grew up in Shijiazhuang, a city that is a two-hour train ride from Beijing. Both his parents were engineers his father worked at the local factory, and his mother built teaching models of traffic systems at a vocational school. His parents worked hard, and like most factory families, they did not have the luxury of looking after their child when school was out.

In the summers, they had to go to work, and they would just lock me at home. Id throw my keys outside to someone to unlock the door so I could go play with them, Guo recalls.

He and his friends would head to a cluster of residential buildings near the factory, and spent their days climbing.

I liked to climb short buildings and towers and look at how they were structured, Guo recalls. There was also a small river where we tried to catch fish. Most families didnt have much savings at the end of the year and didnt spend much effort on education. But I remember as a kid having a lot of fun.

School, and science, came more into focus in high school, when Guo had the chance to visit a cousin who was attending Tsinghua University. He remembers being particularly drawn to a textbook on his cousins shelf, on the structural mechanics of bridges. The short stay inspired him to apply to the university one of the top two schools in the country. Once accepted, he headed to Tsinghua for a degree in mechanics.

After a brief foray into the mechanics of fluids, and a project involving simulations of an artificial blood pump, Guo decided to pivot, and focus instead on the mechanics of cells, plant cells in particular. Inspired by his advisor, he took up the topic of how a plant cells mechanical integrity influences how tall a tree can grow. The project grew into a masters thesis as Guo stayed on at Tsinghua as a masters student.

As I worked on plants, I realized that animal cells were also very interesting, Guo says. The nature of different materials, especially biological materials, and how to understand them simply as physical objects, was fascinating to me.

A profound impact

As he wrapped up his work with tree cells, Guo read up on animal cell research, gravitating to work by David Weitz, a Harvard University physicist who specializes in soft matter, including the mechanical properties of living cells. Weitzs work motivated Guo to apply to Harvards graduate program in applied physics.

In 2007, he arrived on the Cambridge campus the first time hed ever ventured outside China and felt lost amid a new and foreign landscape.

I had filled half my suitcase with ramen, and the first week I just ate ramen because I didnt know where to eat, Guo recalls. I also couldnt understand anything in some of my classes, because the type of English I learned in China was not the way people actually talk here.

After time, Guo found his footing and dove into work in Weitzs lab, where he focused his PhD thesis on understanding the nonequilibrium behavior, or the physical motions in a single cell, and investigating where the energy to generate such motions originates.

That work really shifted my direction, Guo says. I knew what I wanted to do: keep understanding how cell mechanics in multicellular systems like organs and tissues influence everything.

In 2015, he made the move to MIT, where he accepted a junior faculty position in the Department of Mechanical Engineering. At the Institute, he has shaped his research goals around developing new tools and techniques to better study living cells and how their physical and mechanical properties influence how cells move, respond, deform, and function.

In the last few years, weve made some big insights on how, if you change a cells mechanical environment, such as their stiffness or their water content, that has a major impact on some fundamental biochemistry, such as transcription and cell signaling, which in turn regulates multicellular growth, Guo says. So, cell mechanics can have a really profound impact on biology.

In addition to his research, Guo also enjoys teaching MIT students, most recently in 2.788 (Mechanical Engineering and Design of Living Systems), a class that challenges students to apply the mechanics of cells to design novel systems and machines. In a recent class, students have been using cardiac muscle cells to pump liquid through a microfluidic chip. A previous class amplified the natural voltage inside a plant to power a small wheel.

The most energetic and happy moments I have are in talking to students, Guo says. They often give me surprises or new ideas that I love and most look forward to.

In recent years, Guos research and teaching have expanded to consider not just the mechanics of single cells, but also multicellular systems a shift he credits with the arrival of his daughter.

She was born in 2016, and at that time, my entire group was working on single cells, Guo says. But seeing how shes developed, I feel that understanding something that complex is much more interesting. So, we have also started working on exploring the mechanics and mechanobiology of more complex systems such as tissues and embryos.

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How cell mechanics influences everything | MIT News ... - MIT News

Artificial Cells The Powerhouse of the Future – SciTechDaily

Concept of artificial chloroplasts and mitochondria within a liposome for self-sustaining energy generation through photosynthesis and cellular respiration. Credit: Biological Interface Group, Sogang University

Assessing how energy-generating synthetic organelles could sustain artificial cells.

Researchers have assessed the progress and challenges in creating artificial mitochondria and chloroplasts for energy production in synthetic cells. These artificial organelles could potentially enable the development of new organisms or biomaterials. The researchers identified proteins as the most crucial components for molecular rotary machinery, proton transport, and ATP production, which serves as the cells primary energy currency.

Energy production in nature is the responsibility of chloroplasts and mitochondria and is crucial for fabricating sustainable, synthetic cells in the lab. Mitochondria are not only the powerhouses of the cell, as the middle school biology adage goes, but also one of the most complex intracellular components to replicate artificially.

In Biophysics Reviews, by AIP Publishing, researchers from Sogang University in South Korea and the Harbin Institute of Technology in China identified the most promising advancements and greatest challenges of artificial mitochondria and chloroplasts.

This could be an important milestone in understanding the origin of life and the origin of cells. Kwanwoo Shin

If scientists can create artificial mitochondria and chloroplasts, we could potentially develop synthetic cells that can generate energy and synthesize molecules autonomously. This would pave the way for the creation of entirely new organisms or biomaterials, author Kwanwoo Shin said.

In plants, chloroplasts use sunlight to convert water and carbon dioxide into glucose. Mitochondria, found in plants and animals alike, produce energy by breaking down glucose.

Once a cell produces energy, it often uses a molecule called adenosine triphosphate (ATP) to store and transfer that energy. When the cell breaks down the ATP, it releases energy that powers the cells functions.

In other words, ATP acts as the main energy currency of the cell, and it is vital for the cell to perform most of the cellular functions, said Shin.

The team describes the components required to construct synthetic mitochondria and chloroplasts and identifies proteins as the most important aspects for molecular rotary machinery, proton transport, and ATP production.

Previous studies have replicated components that make up the energy-producing organelles. Some of the most promising work investigates the intermediate operations involved in the complex energy-generating process. By connecting the sequence of proteins and enzymes, researchers have improved energy efficiency.

One of the most significant challenges remaining in trying to reconstruct the energy production organelles is enabling self-adaptation in changing environments to maintain a stable supply of ATP. Future studies must investigate how to improve upon this limiting feature before synthetic cells are self-sustainable.

The authors believe it is important to create artificial cells with biologically realistic energy-generation methods that mimic natural processes. Replicating the entire cell could lead to future biomaterials and lend insight into the past.

This could be an important milestone in understanding the origin of life and the origin of cells, Shin said.

Reference: Artificial organelles for sustainable chemical energy conversion and production in artificial cells: Artificial mitochondrion and chloroplasts by Hyun Park, Weichen Wang, Seo Hyeon Min, Yongshuo Ren, Kwanwoo Shin and Xiaojun Han, 28 March 2023, Biophysics.DOI: 10.1063/5.0131071

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Mendus presents an update on the use of its DCOne platform to source high-quality NK cell therapies at the 8th Annual Innate Killer Summit – Yahoo…

Mendus AB

DCONE-DRIVEN EXPANSION OF MEMORY NK CELLS BUILDS THE BASIS FOR NOVEL PROPRIETARY PIPELINE PROGRAM

Mendus AB (Mendus publ; IMMU.ST), a biopharmaceutical company focused on immunotherapies addressing tumor recurrence, today announced that it will present additional data highlighting the use of the companys proprietary DCOne platform for the ex vivo expansion of NK cells today at the 8th Annual Innate Killer Cell Summit in La Jolla, San Diego, CA.

Natural Killer (NK) cells are part of the innate immune system and form a first line of defense against infections and tumor cells. Memory NK cells are associated with improved tumor cell killing and significantly reduced relapse rates in bone marrow-transplanted leukemia patients. Memory NK cells therefore hold great therapeutic promise in the treatment of hematological cancers and potentially other tumor types.

Significant efforts in the NK field have been made to develop superior and reliable expansion methods for NK cells with optimal therapeutic efficacy, including efforts to improve memory phenotype. The NK cell research at Mendus has focused on using our proprietary DCOne platform to improve NK cell quality and specifically on memory NK cells, said Erik Manting, PhD, Chief Executive Officer of Mendus. The DCOne platform provides for an off-the-shelf source of cells which combine cancer cell and dendritic cell biology. Another important aspect of the DCOne cell line is that it is supported by an extensive regulatory dossier and has demonstrated an excellent safety profile in multiple clinical trials.

The data presented today and at SITC 2022 demonstrate that DCOne cells drive strong expansion of memory NK cells, which subsequently can be used in different therapeutic applications. The presence of activating ligands on the cell surface of DCOne-derived mature dendritic cells provide a mechanistic rationale for the observed expansion of memory NK cells with well-characterized molecular signatures.

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The Innate Killer Summit is an industry conference focused on improving patient care by advancing the understanding and enhancing of innate immune cell therapies. On March 30, 3.15pm PST (00:15 CET) Mendus CEO Erik Manting, PhD, will hold a presentation titled Developing Expansion Protocols to Enrich for Memory Phenotypes to Produce Quality over Quantity in Final NK Cell Therapy Products as part of the Clinical Scale Manufacturing track.

During the conference, Dr Manting also chaired a panel discussion titled Sharing a Vision of the Future for Commercial Scale Manufacturing of Innate Immune Cells on March 29.

FOR MORE INFORMATION, PLEASE CONTACT:

Erik MantingChief Executive OfficerE-mail: ir@mendus.com

INVESTOR RELATIONSCorey DavisLifeSci Advisors, LLCTelephone: + 1 212-915-2577E-mail: cdavis@lifesciadvisors.com

MEDIA RELATIONS

Mario BrkuljValency CommunicationsTelephone: +49 160 9352 9951E-mail: mbrkulj@valencycomms.eu

ABOUT MENDUS AB (PUBL)

Mendus is dedicated to changing the course of cancer treatment by addressing tumor recurrence and improving survival outcomes for cancer patients, while preserving quality of life. We are leveraging our unparalleled expertise in allogeneic dendritic cell biology to develop an advanced clinical pipeline of novel, off-the-shelf, cell-based immunotherapies which combine clinical efficacy with a benign safety profile. Based in Sweden and The Netherlands, Mendus is publicly traded on the Nasdaq Stockholm under the ticker IMMU.ST. http://www.mendus.com/

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Mendus presents an update on the use of its DCOne platform to source high-quality NK cell therapies at the 8th Annual Innate Killer Summit - Yahoo...

Basic Science Experts and Information for Media – St. Jude … – St. Jude Children’s Research Hospital

Basic science also called bench research provides a foundation of understanding upon which clinical breakthroughs are built. Basic science can be used to uncover the mechanisms behind the functioning of the human body. Once these fundamentals are understood, the findings may be translated into patient care, completing the bench-to-bedside journey. Basic science departments and divisions at St. Jude include Cell and Molecular Biology, Chemical Biology, Developmental Neurobiology, Immunology, Infectious Disease, Structural Biology and Tumor Cell Biology.

To schedule an interview with one of our experts, email media@stjude.org.

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Basic Science Experts and Information for Media - St. Jude ... - St. Jude Children's Research Hospital

Researchers reveal structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT – Phys.org

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In a study published in Science Advances, Dr. Cong Yao's team from the Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, reported a complete picture of TRiC-assisted tubulin/actin folding along TRiC ATPase cycle under the coordination of co-chaperone plp2 through cryoelectron microscopy (cryo-EM) analysis.

The eukaryotic group II chaperonin TRiC/CCT assists the folding of ~10% of cytosolic proteins through ATP-driven conformational circle, including many key structural and regulatory proteins, such as the key cytoskeletal proteins tubulin and actin, the cell cycle regulator CDC20 and many proteins involved in oncogenesis. Thus, TRiC plays an essential role in maintaining cellular protein homeostasis. Dysfunction of TRiC is closely related to cancer and neurodegenerative diseases.

The major cytoskeletal proteins tubulin and actin are obligate substrates of TRiC. A remarkably complex cellular machinery consisting minimally of TRiC, cochaperone, and cofactors has evolved to facilitate their biogenesis. It has been shown that phosducin-like protein 2 (PhLP2) is essential for ciliogenesis and microtubule assembly, and the ciliary precursor tubulin needs to be folded by TRiC with assistance of PhLP2.

The researchers first determined an ensemble of cryo-EM structures of S. cerevisiae TRiC along its ATPase cycle, with simultaneously engaged plp2 and substrate actin or tubulin inside its chamber, one per ring, at the resolution of up to 3.05 , In the open S1/S2 states, plp2 and tubulin/actin engaged within opposite TRiC chambers, and the substrate density remains less well resolved, indicating that it might be in the initial stage of folding.

Intriguingly, the researchers captured an unprecedented TRiC-plp2-tubulin complex in the closed S3 state, engaged with a fully folded full-length -tubulin which even loaded with a GTP since its "birth" from the TRiC chamber, and a plp2 occupying the opposite ring. This provides new clues for the biogenesis of tubulin and the assembly of a/b-tubulin heterodimers. Another closed S4 state revealed an actin in the intermediate folding state and a plp2.

Accompanying TRiC ring closure, plp2 translocation in one ring could coordinate substrate translocation on the CCT6 hemisphere of the opposite ring, facilitating substrate stabilization and folding. In addition, the co-chaperone plp2 engages within the cavity of TRiC regardless of the TRiC conformational state, but other co-chaperones of TRiC such as PFD and PhLP1 were observed only bound on the outer top of the open TRiC ring.

This study provides structural insights into the folding mechanism of the major cytoskeletal proteins tubulin/actin under the coordination of the complex biogenesis machinery TRiC and plp2, and could extend the understanding on the links between cytoskeletal proteostasis and related human diseases such as developmental and neurological disorders.

More information: Wenyu Han et al, Structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT, Science Advances (2023). DOI: 10.1126/sciadv.ade1207

Journal information: Science Advances

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Researchers reveal structural basis of plp2-mediated cytoskeletal protein folding by TRiC/CCT - Phys.org

Labroots Announces Full Agenda for its 5th Annual Bioprocessing … – PR Web

Bioprocessing Virtual Event Series, April 5, 2023

YORBA LINDA, Calif. (PRWEB) March 30, 2023

Labroots, the leading scientific social networking website, which offers premier, interactive virtual events and webinars to the scientific community, is delighted to host its Bioprocessing Virtual Event Series scheduled on April 5, 2023. Marking its 5th year, this premier global forum comprises drug discovery and preclinical development, upstream processing, downstream processing, analytical development and quality, cell, gene, and nucleic therapies (novel modalities), and manufacturing track sessions.

Free to attend, the program gathers prominent experts from leading academia and industry institutions, top scientists, and research scholars to present the latest advancements on how to accelerate promising biologics and cell and gene therapies, and improve efficiencies spanning all facets of biopharmaceutical development and production.

The jam-packed agenda showcases over 15 sponsored and educational in-depth presentations with multiple live Q&A sessions spanning optimizing clone selection in cell line development, human-induced pluripotent stem cell expansion in a stirred 3D system and the importance of process monitoring, an automated process analytical platform to enable continuous manufacturing of biologics, antibody purification via the unconventional nucleotide binding site, 3D visualisation and characterisation of downstream bioprocessing structures to inform advanced designs, engineering and reprogramming natural killer cells for immunotherapy of cancer, and how digital bioprocess twins can accelerate process development and enable model predictive control strategies, plus much more!

A few conference highlights include two keynote deliveries and panel presentations:

Gene therapy-based medicines have opened new doors for the treatment and cure of genetic disease, said Baley Reeves, PhD, Interim Director, National Center for Therapeutics Manufacturing, Texas A&M Engineering. However, a generic manufacturing platform for gene therapy products has yet to be developed. Information sharing via Labroots platform will be critical as we shape the future for how therapeutics are made.

"I will present data about a pioneering expression system developed by my group at the university of Kent that improves yield, speed and efficiencies in the biotechnology industry to create proteins in bacteria, said Dan Mulvihill, PhD, Professor, Cell and Molecular Biology at the University of Kent. "This new technology enables scientists to reprogram a cell to direct the packaging of specific molecules into a separate structure, known as a vesicle, which is then exported out of the cell. This patented technology will improve efficiencies in creating and storing recombinant proteins, which have a range of uses from antibodies to energy production, and I'm delighted to share this technology via Labroots' unique platform."

Produced on Labroots robust platform, this online event allows participants to connect seamlessly across all desktop and mobile devices providing a complete educational experience. The interactive environment includes a lobby equipped with a leaderboard and gamification, an auditorium featuring live-streaming video webcasts with live attendee chats during scheduled presentations, an exhibit hall to interact with sponsors highlighting contributions in the field, a poster hall to explore data while engaging in live chat conversations coupled with a poster competition giving your research a competitive edge and lastly, a networking lounge to encourage collaborations with colleagues.

Labroots is approved as a provider of continuing education programs in the clinical laboratory sciences by the ASCLS P.A.C.E. Program. By attending this event, Continuing Education credit (1 per presentation) can be earned for a maximum of 35 credits.

To register for this free event, click here. Use #LRbioprocessing to follow the conversation and connect with other members of the global Bioprocessing community! Follow bioprocessing-related pages @CellBiology_LR on Twitter and @CellandMolecularBiology.LR on Facebook to connect with our specialist Cell Biology Sciences Writers and stay up to date with the latest Trending News in Cell Biology!

About Labroots Labroots is the leading scientific social networking website and primary source for scientific trending news and premier educational virtual events and webinars, and more. Contributing to the advancement of science through content sharing capabilities, Labroots is a powerful advocate for amplifying global networks and communities. Founded in 2008, Labroots emphasizes digital innovation in scientific collaboration and learning. Offering more than articles and webcasts that go beyond the mundane and explore the latest discoveries in the world of science, Labroots users can stay atop their field by gaining continuing education credits from a wide range of topics through their participation in the webinars and virtual events. Labroots offers more than ever with Chati, a flexible, highly scalable event platform that allows for the creation of unique, effective, and memorable virtual events.

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RoslinCT and Lykan Bioscience announce that the MHRA has granted an MIA License for their cGMP Manufacturing facilities in Edinburgh, UK – Yahoo…

EDINBURGH, U.K. and HOPKINTON, Mass., March 30, 2023 /PRNewswire/ -- RoslinCT and Lykan Bioscience, leaders in ground-breaking Contract Development and Manufacturing for cell therapies, are delighted to announce that following a successful inspection at their Edinburgh, UK facility, from the Medicines and Healthcare products Regulatory Agency (MHRA), a Manufacturer's Authorisation Licence (MIA) for commercial manufacturing of cell therapy products has been granted.

RoslinCT_Lykan

Completed in late 2021, RoslinCT's newest 1,600 square-meter state-of-the-art facility,located in Edinburgh's BioQuarter, was designed to operate as a flexible and scalable manufacturing hub, housing five cGMP clean rooms and a dedicated training laboratory.The cGMP facility has been designed and purpose-built specifically to accommodate cell therapy manufacturing processes for both allogeneic and autologous therapies with or without genome editing requirements.

The license granted by the UK's regulatory body will allow RoslinCT and Lykan Bioscience, who are currently working with their partners to develop and manufacture cutting edge life-changing therapies and cures for patients suffering from some of the most debilitating medical conditions, to expand their service offering to produce market-approved cell therapy products.

Peter Coleman, Chief Executive Officer of RoslinCT said:"At RoslinCT we thrive on being pioneers in our sector, accelerating the delivery of these novel life-changing therapies to patients. The MIA commercial manufacturing licence is a huge landmark in the history of RoslinCT and is testament to the relationship we have developed with the MHRA and the hard work of our team. We will continue to work with our partners to deliver these life-saving therapies to patients".

Patrick Lucy, President & Chief Executive Officer of Lykan Bioscience, commented:"This license is a significant milestone for RoslinCT, Lykan Bioscience and our partners. Empowering our partners to progress efficiently from development to commercialization and deliver life-saving cell therapies to patients worldwide is at the core of our mission. The learnings acquired by RoslinCT that ultimately resulted in the receipt of the commercial manufacturing license will be invaluable as we align our global manufacturing operations".

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About RoslinCT

RoslinCT is a leading UK Cell Therapy Contract Development and Manufacturing Organisation (CDMO) focused on providing services for companies developing cell-based therapeutic products. Originally founded in 2006 as a spin-out from the Roslin Institute, RoslinCT expanded the broad range of scientific expertise available in the field of cell biology. Based at the Edinburgh BioQuarter, the company operates fully licensed GMP manufacturing facilities and has a proven track record in delivering cell-based products. For further information, please visit http://www.roslinct.com.

About Lykan Bioscience

Lykan Bioscience is an innovative contract development and manufacturing services organization (CDMO) focused on cell-based therapies. With decades of biopharmaceutical industry experience, Lykan offers a full range of development and manufacturing services. The state-of-the-art, purpose-built facility offering 14 independent manufacturing suites is uniquely designed to fully integrate cGMP principles and advanced software solutions to enable real-time testing, US/EU clinical and commercial manufacturing and release of product. Located in Hopkinton, Massachusetts, 25 miles southwest of downtown Boston and in the proximity of four international airports, Lykan Bioscience is ideally situated to deliver life-saving cell therapy treatments to patients on behalf of their partners. Visit http://www.lykanbio.com

For Media Enquiries

RoslinCT Marketing ManagerKaterina Tsita katerina.tsita@roslinct.com

Lykan Bioscience Senior Director of Marketing Carrie Zhang carrie.zhang@lykanbio.com

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‘ASBMB opened the doors for me’ – ASBMB Today

A fellow student first drew Clarissa Nuez to the American Society for Biochemistry and Molecular Biology Student Chapter at New Mexico State University. After hearing a classmate promote the ASBMB in her first year, Nuez started showing up to meetings and never looked back. Before her graduation last year, she served as a secretary, president and vice president of the chapter.

Coming into college from her hometown of Las Cruces, New Mexico, Nuez knew she enjoyed science and was excited to learn about how life works at the molecular level. At New Mexico State, she went through a process of elimination to find her major, ultimately deciding on biochemistry with a minor in molecular biology.

Robert Hood, Fred Hutchinson Cancer Research Center

Clarissa Nuez joined the ASBMB Student Chapter in her first year at New Mexico State University. Now shes pursuing a Ph.D. in cell and molecular biology at the University of Texas Southwestern.

Science didnt seem like a potential career until she joined the ASBMB Student Chapter, Nuez said. It was there that she heard from other students working in research labs, helped host events such as career development talks and scientist panels, and found out about the National Institutes of Health Maximizing Access to Research Careers, or MARC, fellowship, which helps fund undergraduate degrees while encouraging hands-on research experience. She successfully applied to the MARC program, and it became another cornerstone of her college experience.

Through both the ASBMB chapter and MARC, Nuez found a community of like-minded peers and new ways to explore science. Classmates became friends with whom she could study, talk about and do research, and eventually go through the graduate school application process.

MARC also gave her great female and Hispanic mentors, including the two scientists who led the program.

It unlocked a whole new layer of the university, the science community on campus that I would not have been exposed to if I didnt attend the meetings, she said of the Student Chapter.

As part of the MARC fellowship, Nuez worked on an independent project in Brad Shusters lab for her last two undergrad years. Her work focused on the protein PRC1 and its role in cell division, and she said this experience taught her fundamental lab skills in addition to being, in her words, a really fun project.

Another formative research opportunity was an internship at the Fred Hutchinson Cancer Research Center, where she got to work in the lab full time. With all this training under her belt, Nuez realized she had a passion for research.

As I had these experiences, and as they wrapped up, I think I just realized the thing I wanted to do most was work in a research lab forever, she said, adding that she asked herself, Whats one way I can be challenged to improve those skills and really become a rigorous scientist?

For her, the answer was graduate school, and Nuez now is situated happily at the University of Texas Southwestern pursuing a Ph.D. in cell and molecular biology. Looking back on her academic journey, she said her commitment to the ASBMB chapter was key. From the challenges of being president to the joys of scientific outreach, from her initial uncertainty about a graduate degree to taking that leap of faith, the community she found within the ASBMB has been a guiding force.

I think just having that experience in undergrad really opened so many doors for me, she said, and honestly, I dont think Id be where Im at if I had not been a member, as cheesy as that sounds. It really did open a lot of connections, and mentorship, and different things that paved the way to where I am now.

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More Fun Than Fun: Science Is Impoverished Without Its Tales – The Wire Science

Cell cultural flasks of Peyton Rous, circa 1936. Photo: Lubosh Stepanek, Courtesy of the Rita and Frits Markus Library, The Rockefeller University

I spent the second half of the 1970s at the Microbiology and Cell Biology Laboratory at the Indian Institute of Science, Bengaluru, immersed in studying the lysogenic mycobacteriophage I3. Bacteriophages are viruses that infect bacteria and use the host bacterial machinery to make copies of themselves. This one infects Mycobacteria, hence it is a mycobacteriophage. Lytic bacteriophages burst open the host-bacterium to release their offspring, infecting other healthy bacteria and continuing the cycle. On the other hand, lysogenic bacteriophages have a dual strategy: they can either follow the lytic life cycle right away or lie low for many bacterial generations before they make copies of themselves and burst the host cell.

As I have described in more detail elsewhere and repeat here in part, as an undergraduate at Central College, I fell in love with two subjects animal behaviour and molecular biology, neither of which were taught with any degree of passion or competence by my teachers. My love for animal behaviour was born from reading King Solomons Ring by the Nobel laureate Konrad Lorenz and sustained by my discovery of many colonies of the Indian paper wasp Ropalidia marginata on the windows of the zoology and botany departments. And my love for molecular biology was born from reading The Double Helix by another Nobel laureate, James D. Watson and was sustained by my discovery in the pages of journals in the library, of an exquisite organism, the lysogenic bacteriophage Lambda. But I soon found the local avatar of the bacteriophage lambda. One day, I jumped up from my chair in the library when I read in the pages of Nature [Vol 228, October 17, 1970] that C.V. Sunder Raj of the Microbiology and Pharmacology Laboratory of the Institute had discovered our very own Indian lysogenic bacteriophage. I promptly came to see him, and he showed me beautiful Petri plates in which the mycobacteriophage I3 had made transparent holes on a lawn of the bacterium Mycobacterium smegmatis. The I in I3 was meant to denote Isolate 3, but I had no qualms about thinking of the I as indicating India.

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In 1974, at the age of 21, I was lucky enough to be admitted to a single vacancy in the interdisciplinary field of molecular biology. I joined the by-now re-christened, Microbiology and Cell Biology Laboratory for my PhD. I spent the next five years studying the alter ego of bacteriophage lambda, our own bacteriophage I3. Imagine my delight when I saw that the Institute campus was also home to innumerable colonies of my other love, the Indian paper wasp R. marginata. During the next five years, I made bacteriophage I3 the subject of my professional study, and the paper wasp R. marginata the subject of my hobby.

As I began my PhD enthusiastically on my favourite kind of bacteriophage, while my supervisor was away on a sabbatical leave abroad, I already encountered a major roadblock. To obtain large quantities of any bacteriophage, it is routine practice to grow the host bacteria in flasks, infect them with a small quantity of the bacteriophage, and let the bacteriophage multiply.

The author conducting experiments during his PhD at the Microbiology and Cell Biology Laboratory, Indian Institute of Science, Bangalore, 1974-1979.

In my case, the host bacterium of I3 was Mycobacterium smegmatis which our laboratory was able to grow in flasks, but I3 would not grow in the flasks. The only way to grow I3 was on a lawn of the host bacterium on small Petri plates, but this was a very tedious and laborious procedure. So, I made it my first challenge to make I3 grow in the flasks. After some very exciting detective work and testing many hypotheses, I discovered that the culprit was the detergent Tween-80 which was routinely added to the culture medium to prevent M. smegmatis from clumping together. I was even able to show that in the presence of Tween-80, the bacteriophage was able to adsorb onto the bacteria but could not inject its DNA into the host. And once allowed to inject its DNA, it then grew well even if Tween-80 was added later. Thus, I was able to grow large quantities of I3 by delaying the addition of Tween-80 after the bacteriophage had injected its DNA into the host bacterium. This was a great lesson in taking on a roadblock as a challenging part of the research. Being already of an ecological and evolutionary bent of mind, I went on to investigate such questions as how different individual bacteriophages cooperated and competed with each other when they were inside the host bacterium.

One floor below my laboratory, a dear friend Arun Srivastava was similarly engaged in studying the Rous Sarcoma Virus (RSV). While my main aim was to get my bacteriophages to grow as rapidly as possible, Aruns main aim, contrarily, was to find ways of inhibiting the growth of his viruses, at least in cell cultures. The reason for this is obvious, of course, because RSV is a tumour-causing virus, and the discovery of drugs that could slow or inhibit viral growth would have great potential in cancer treatment. Arun had a novel approach. His mentor professor T. Ramakrishnan had been working on Isoniazid, a potential anti-tubercular drug. A unique property of isoniazid is that it binds to metals. The enzyme reverse transcriptase (see below), which helps RSV to reproduce, had recently been shown to contain zinc. The idea was to see if isoniazid inactivated the reverse transcriptase by binding to its zinc. In a recent issue of Resonance journal of science education published by the Indian Academy of Sciences, Arun Srivastava has given a moving account of that research. Arun Srivastava is now Division Chief and George H. Kitzman Professor at the Department of Pediatrics in the College of Medicine, University of Florida, US. Dr Arun Srivastava at the lab workbench attempting to infect HeLa cells with a genome-modified adeno associated virus (AAV) in search of more effective gene therapy on March 22, 2023. Photo courtesy: Arun Srivastava

Arun and I, and a few other PhD-mates, were mesmerised by the viruses, both bacterial and animal. We lived and dreamed of phages and viruses and read every printed page we could find about, T4, X174, RSV, RPV and NDV, as much in love with their names as with their biology and life cycles, their replication and coat proteins, their prophages and proviruses. In our youthful exuberance, we believed we knew nearly everything about these magical creatures, which were so charmingly neither alive nor dead. How wrong we were!

We did not know their tales. This I realised only after reading A Tale of Two Viruses by Neeraja Sankaran. Reading Neerajas book was a fortuitous event because I got an invitation, out of the blue, from a little-known (at least to me) online publication called Inference to review Neeraja Sankarans book, which I did with great pleasure. Some of what I write below is reproduced with permission from my article in Inference. The Oxford English dictionary defines a tale as a narrative or story, especially one that is imaginatively recounted. A Tale of Two Viruses fits this definition well. Neeraja Sankarans principal imaginative contribution is to draw parallels between the tales of her two protagonists, the bacteriophages, and the Rous Sarcoma Virus (RSV), my and Aruns study subjects, as it happens. Her juxtaposition of these two tales adds value and colour to each protagonists tale and creates a whole new tale.

Neerajas tale begins in about the second decade of the 20th century with the discovery of bacteriophages and RSV and extends forward by about half a century. But our journey with her is neither restricted to this period nor do we traverse the period chronologically. We are taken back several centuries before the present to set the context and ferried back and forth across time to benefit from hindsight. But because her narrative structure is so clearly explained in the Introduction, we are never lost. Neeraja Sankaran and her book A Tale of Two Viruses,published by the University of Pittsburgh Press in (2021).

Neeraja opens with an inspired description of the birth pangs of RSV at the hands of Peyton Rous, an American pathologist working at Rockefeller University in New York, and of bacteriophages at the hands of Frederick Twort, a medical researcher in London and Flix dHerelle, a kind of free-lance scientist working at the Pasteur Institute in Paris. With all these three pioneers, it appears that they themselves were more on the right track than most of their peers in understanding the nature of the substances they had found; so much for peer review! Two anecdotes especially struck me as they illustrate two contrasting benefits of paying attention to the history of science.

A young Peyton Rous, who won the Nobel Prize in Physiology or Medicine in 1966for his discovery of tumour-inducing viruses, was advised by his distinguished mentor William Welch whatever you do, do not commit yourself to the cancer problem. A knowledge of history might make some of us a little more modest in our confidence in predicting the future and especially in second-guessing the abilities of our young mentees. In an apparent act of carelessness, Simon Flexner, the founding director of the Rockefeller Institute, attributed the early discovery of RSV jointly to Rous and his former assistant, James B. Murphy. Rous wrote in protest:

You said that Rous and Murphy demonstrated the existence of the filterable agent causing the chicken tumour. Now, the fact is that I carried out this work alone and published alone two papers that embodied its resultsMurphy had no hand in the experimental episode which showed an infinitely little agent to be the cause of the tumour

By paying attention to history, some of us might empathise with Rouss agony and take comfort in our sense of dj vu, while others among us might become more sensitive directors.

The fact that a virus was an entirely new kind of entity, defying the boundary between the living and the non-living, adds much drama to the tales of RSV and bacteriophages, a drama that is captured in rich detail in A Tale of Two Viruses. If we put aside the benefit of hindsight, we can understand the incredulity of scientists and doctors of that era. They must have found it hard to imagine that an invisible substance that causes disease is not a mere protein or enzyme but rather a living agent that copied itself. I find it instructive to think how I might have fared in such a situation, which in turn makes me wonder whether I am already in a comparable situation regarding modern incredulities and future revelations.

Neeraja then takes us on a romp through the saga of the coming of age and the acceptance of bacteriophages and RSV as viruses. Neeraja is at her meticulous historical best in the chapter on bacteriophages, as this is based on her doctoral thesis. I particularly appreciated the light she shines on Frank Macfarlane Burnetswork on bacteriophages, which in my mind had been overshadowed by his Nobel Prize-winning work in immunology, predicting acquired immune tolerance and developing the theory of clonal selection. I was fascinated by Neerajas refreshingly new perspective on the role of Max Delbrck and the American. L-R: Peyton Rous, an American pathologist working at Rockefeller University in New York, 1911. Photo: Unknown; Non-Exclusive Unrestricted License, Courtesy: Olga Nilova; Frederick Twort, a medical researcher in London. Photo:Obituary Notices of Fellows of the Royal Society, Public Domain;Flix dHerelle, a kind of free-lance scientist working at the Pasteur Institute in Paris. Photo: Service photo Institut Pasteur, Public domain

Phage Group in the history of the concept of bacteriophages as viruses, especially because my previous reading had been dominated by their role in the history of molecular biology. It is just as well that the coming of age of the bacteriophages and RSV are treated in separate chapters because the contexts in which the two fields matured are so different. The way I see it, bacteriophages (along with their host bacteria, of course) played a pivotal role in establishing molecular biology on firm ground, all the way up to Francis Cricks central dogma; the dogma states that information can only flow from DNA to RNA to protein and not in reverse. Perhaps we should call this the fairy tale stage. On the other hand, RSV (along with its eukaryotic host cells, of course), with the discovery of reverse transcriptase and violation of at least one part of the central dogma, took centre stage in taking molecular biology out of the fairyland and making it real, complex, and messy.

In what she describes as her second intermezzo, Neeraja shows how the development of new technologyultracentrifugation, electron microscopy, X-Ray crystallography and morehelped the scientific community to select among previously held ideas about the nature of substances that somewhat mysteriously possessed the magical properties that define a virus. I admit to a sense of awe at what these technologies could do and how they were developed with great human ingeniousness and a running collaboration between scientists and engineers. Nevertheless, I must confess my prejudicemy greater awe at what scientists could imagine, postulate, and tease out in their minds without the aid of soon-to-be-available prosthetics. I have the greatest admiration for the developers of technology, the developers of ideas, and designers of experiments without the aid of technology, and a wee bit less for refining old ideas with new technology.

For me, one of lifes greatest pleasures is to read the older scientific literature and admire how people thought about complex issues and designed ingenious experiments, using the kind of ingeniousness that seems obsolete in the light of present-day technology. Early experiments in classical genetics using the fruit fly Drosophila melanogaster yield some of the finest examples of ingenuity untrampled by too much knowledge and too much technology, elegantly described by Richard C. Lewontin in his The Genetic Basis of Evolutionary Change (1974). I believe that this very kind of obsolete ingeniousness will be necessary for us to be creative today before the next-generation technology makes it obsolete again. I have a kind of supremacy of mind over instruments prejudice. That is why I admire more the engineers who made the instruments than the scientists who use them. My twin heroes are the engineers who make sophisticated instruments and the scientists who make do without them!

I found Neerajas chapter, Lysogeny as Linchpin, the most interesting. This must be partly because of my great love for lysogenic bacteriophages, one of which, as I described above, was the subject of my PhD thesis. But there is more. As an evolutionary biologist, I cant help admiring the smartness of lysogenic bacteriophages. The other kind, so-called lytic bacteriophages, inject their DNA or RNA into a host cell, subvert the host machinery to make more copies of themselves, burst open the host cell and escape to find more hosts. Lysogenic bacteriophages can and do all of this, but do so only if the host seems healthy enough to make this option profitable. If the host bacterium is a bit impoverished, it will lie low for a while and try later. Meanwhile, it will, of course, integrate its DNA into the host DNA so that as the host divides, all their daughters will carry a copy of its DNA the so-called prophage. When some of the bacteria appear to be in good health, the prophage will exit and switch to the lytic mode, i.e., make more copies of the bacteriophage and burst the host cell.

I have long wondered why the host carries the burden of the prophage, including the cost of replicating it in every generation, not to mention the ever-present danger that it will exit and kill it one day. Not surprisingly, there is now growing evidence that the host benefits in many ways by harbouring the prophage. One somewhat obvious advantage is that because the ability to make copies of the phage is temporarily repressed, the host is also unsuitable for making copies of other super-infecting bacteriophages that might use this cell. The prophage thus confers immunity to the host from other bacteriophages. Even more interesting is the suggestion that the prophage might help the host to tide over conditions of low nutrition. This is interesting because the death of the host also means the end of the prophage. No wonder the prophage is especially concerned about the welfare of its host in a dire situation. So much for why I love the phenomenon of lysogeny. Neerajas interest is very different but equally interesting.

In the early history of bacteriophages, the phenomenon of lysogeny appeared to be the strongest argument against the theory that bacteriophages were viruses. The Belgian microbiologist and Nobel Laureate, a staunch opponent of the virus theory of bacteriophages proposed by Twort and dHrelle, claimed that The invisible virus of dHrelle does not exist. One ground for his disbelief was that he found it impossible to imagine that the lysogenic bacteria had harboured viruses for generations without manifesting any signs of infection and that it suddenly underwent lysis due to the action of those selfsame viruses.

As Neeraja Sankaran has argued, the true meaning of lysogeny could not be fathomed by all but the most astute or the luckiest of scientists before the chemical nature of the genetic material and the basics of molecular biology were understood. In any case, after the famous Avery, MacLeod, and McCarty demonstration of DNA as the hereditary material in 1944, it became clear, especially from the work of the French microbiologist Andr Lwoff that the invisible virus does exist in the form of a prophage. It also became clear how the host cells suddenly underwent lysis due to the action of those selfsame viruses. Ironically, this clarification thus became the strongest argument in favour of the virus theory of bacteriophages. As if this were not enough, understanding that lysogenic bacteriophages remain dormant as prophages in the DNA of their host bacteria paved the way for accepting the idea that tumour viruses such as RSV could do the same by making proviruses instead of prophages. And because RSV is an RNA virus, its RNA has to be first copied into DNA before it can be integrated into the host DNA an invitation to violate the central dogma of molecular biology and the inevitable discovery of reverse transcriptase. Little wonder that Neeraja calls lysogeny the lynchpin of her tale of two viruses. I find all this incredibly beautiful and enriching.

Almost everything Neeraja Sankaran describes in A Tale of Two Viruses (not including the new knowledge she has created in retelling these tales) had already transpired before the mid-1970s. How I wish Arun and I had heard these tales while studying bacteriophages and RSV for our PhD. Rich as it was, our intellectual life would have been so much more enriched by studying the history of our study objects. I am surprised that scientists pay little more than lip service to the history of science. Personally, I find that while textbooks, monographs and research papers give me the bricks to build, only the history of science and biographies and autobiographies of scientists can provide me with the cement to glue the bricks together and construct a stable and coherent edifice. This truth is brought home to me repeatedly when I read books such as A Tale of Two Viruses by Neeraja Sankaran, The Monk in the Garden by Robin Marantz Henig, Unravelling the Double Helix by Gareth Williams, The Transforming Principle by MacLyn McCarty, Defenders of the Truth by Ullika Segerstrale, Genes, Germs and Medicine by Jan Sapp, The Atomic State by Jahnavi Phalke, to name some of my most recent pickings.

History informs practising scientists of how and why the questions and techniques they pursue came to be privileged over others and how ideas and theories rise and fall with time. Even more importantly, a historical perspective gives us a sense of purpose and a feeling that we are part of a grand narrative. It helps make the pursuit of science a hobby and a passion rather than a mere job. I believe science pursued without the benefit of the kind of historical perspective gained from reading A Tale of Two Viruses, for example, is significantly impoverished.

Lorraine Daston, director emerita at the Max Planck Institute for the Historyof Science, Berlin has argued most persuasively and with welcome provocativeness that scientists need to pay attention to the history of their discipline. She said in a recent interview:

because of the combination of the narrowness of research specialization and the intense pressure to produce results quickly, they [scientists] have no overview of their field. Or perhaps to put it more provocatively, they dont know why theyre working on what theyre working on. Moreover, they dont know what the alternatives are. The history of science has always served two purposes. One purpose has been to give that kind of orientation Heres how the field has developed; this is why it has taken this path rather than another path Another use, of course, is to prepare scientists for decisions that no science textbook can prepare them for, namely, ethical decisions.

If I complain about scientists not paying attention to history, I also sometimes complain about historians of science paying too much attention to who writes history. They make too big a deal of what they call the insider-outsider problem. I can see that those formally trained in history and teach themselves science will write a different kind of history than those formally trained in science and teach themselves how to do history. But I believe we need both types of histories unless we are fortunate to have someone like Neeraja Sankaran, who first trained as a microbiologist [BSc (Hons)], Punjab University) and later trained as a historian (PhD, Yale). Let there be more of her kind.

Raghavendra Gadagkar is a Department of Science and Technology (DST) Year of Science Chair Professor at the Centre for Ecological Sciences at the Indian Institute of Science, Bengaluru.

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More Fun Than Fun: Science Is Impoverished Without Its Tales - The Wire Science