Category Archives: Cell Biology

Cell Biology

Adding intrinsically disordered proteins to biological ageing clocks – Nature.com

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Adding intrinsically disordered proteins to biological ageing clocks - Nature.com

Cell Biology

Advancing Cell Biology and Cancer Research via Cell Culture and Microscopy Imaging Techniques – Lab Manager Magazine

Tech Trends Webinar

Tuesday, June 25, 2024 1 PM EDT

Cell culture is a fundamental technique in biology and biotechnology that involves the growth and maintenance of cells outside their natural environment, typically in a laboratory setting. Cells can be cultured from various sources, including animal tissues, plants, fungi, and bacteria. Cell culture techniques are widely used in various fields, including basic research, drug discovery, regenerative medicine, and biotechnology. They allow researchers to study cell behavior, function, and interactions in controlled conditions, providing insights into biological processes and disease mechanisms. Additionally, cell culture is essential for producing biological products like vaccines, therapeutic proteins, and tissue-engineered constructs for transplantation.

Cell culture and microscopy imaging are integral to biological research, with microscopy enabling high-resolution visualization and analysis of cellular structure, function, and behavior. Techniques such as live cell imaging allow researchers to directly observe cell health and growth patterns in real time. Meanwhile, fluorescence microscopy provides detailed views of specific cellular structures and organelles, helping to elucidate cellular interactions and the impact of environmental changes on biological systems. Additionally, microscopy imaging is extensively used to examine cellular responses to treatments, thereby aiding in the development of new therapeutic approaches and medical diagnostics.

Overall, the combination of cell culture and microscopy imaging is essential for advancing our understanding of cell biology, disease mechanisms, and drug development. It enables researchers to observe and analyze cellular processes with high precision and detail, leading to discoveries that drive scientific progress and innovation.

Zulin Yu Head of Light Microscopy Stowers Institute

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Advancing Cell Biology and Cancer Research via Cell Culture and Microscopy Imaging Techniques - Lab Manager Magazine

Cell Biology

Study explores how different modes of cell division evolved in close relatives of fungi and animals – News-Medical.Net

Cell division is one of the most fundamental processes of life. From bacteria to blue whales, every living being on Earth relies on cell division for growth, reproduction, and species survival. Yet, there is remarkable diversity in the way different organisms carry out this universal process. A new study from EMBL Heidelberg's Dey group and their collaborators, recently published in Nature, explores how different modes of cell division evolved in close relatives of fungi and animals, demonstrating, for the first time, the link between an organism's life cycle and the way their cells divide.

Despite last sharing a common ancestor over a billion years ago, animals and fungi are similar in many ways. Both belong to a broader group called 'eukaryotes' organisms whose cells store their genetic material inside a closed compartment called the 'nucleus'. The two differ, however, in how they carry out many physiological processes, including the most common type of cell division mitosis.

Most animal cells undergo 'open' mitosis, in which the nuclear envelope the two-layered membrane separating the nucleus from the rest of the cell breaks down when cell division begins. However, most fungi use a different form of cell division called 'closed' mitosis in which the nuclear envelope remains intact throughout the division process. However, very little is known about why or how these two distinct modes of cell division evolved and what factors determine which mode would be predominantly followed by a particular species.

This question captured the attention of scientists in the Dey Group at EMBL Heidelberg, who investigate the evolutionary origins of the nucleus and cell division.

By studying diversity across organisms and reconstructing how things evolved, we can begin to ask if there are universal rules that underlie how such fundamental biological processes work."

Gautam Dey, Group Leader at EMBL Heidelberg

In 2020, during the COVID-19 lockdown, an unexpected path to answering this question grew out of discussions between Dey's group and Omaya Dudin's team at the Swiss Federal Institute of Technology (EPFL), Lausanne. Dudin is an expert in an unusual group of marine protists Ichthyosporea. Ichthyosporea are closely related to both fungi and animals, with different species lying closer to one or the other group on the evolutionary family tree.

The Dey and Dudin groups, in collaboration with Yannick Schwab's group at EMBL Heidelberg, decided to probe the origins of open and closed mitosis using Ichthyosporea as a model. Interestingly, the researchers found that certain species of Ichthyosporea undergo closed mitosis while others undergo open mitosis. Therefore, by comparing and contrasting their biology, they could obtain insights into how organisms adapt to and use these two cell division modes.

Hiral Shah, an EIPOD fellow working across the three groups, led the study. "Having recognized very early that Ichthyosporea, with their many nuclei and key evolutionary position between animal and fungi, were well-suited for addressing this question, it was clear that this would require bringing together the cell biological and technical expertise of the Dey, Dudin, and Schwab groups, and this is exactly what the EIPOD fellowship allowed me to do," said Shah.

Upon closely probing the mechanisms of cell division in two species of Ichthyosporeans, the researchers found that one species, S. arctica, favours closed mitosis, similar to fungi. S. arctica also has a life cycle with a multinucleate stage, where many nuclei exist within the same cell another feature shared with many fungal species as well as the embryonic stages of certain animals, such as fruit flies. Another species, C. perkinsii, turned out to be much more animal-like, relying on open mitosis. Its life cycle involves primarily mononucleate stages, where each cell has a single nucleus.

"Our findings led to the key inference that the way animal cells do mitosis evolved hundreds of millions of years before animals did. The work therefore has direct implications for our general understanding of how eukaryotic cell division mechanisms evolve and diversify in the context of diverse life cycles, and provides a key piece of the animal origins puzzle," said Dey.

The study combined expertise in comparative phylogenetics, electron microscopy (from the Schwab Group and the electron microscopy core facility (EMCF) at EMBL Heidelberg), and ultrastructure expansion microscopy, a technique that involves embedding biological samples in a transparent gel and physically expanding it. Additionally, Eelco Tromer, from the University of Groningen in the Netherlands, and Iva Tolic, from the Ruer Bokovi Institute in Zagreb, Croatia, provided expertise in comparative genomics and mitotic spindle geometry and biophysics, respectively.

"The first time we saw an expanded S. arctica nucleus, we knew this technique would change the way we study the cell biology of non-model organisms," said Shah, who brought back the expansion microscopy technique to EMBL Heidelberg after a stint at the Dudin lab. Dey agrees: "A key breakthrough in this study came with our application of ultrastructure expansion microscopy (U-ExM) to the analysis of the ichthyosporean cytoskeleton. Without U-ExM, immunofluorescence and most dye labelling protocols do not work in this understudied group of marine holozoans."

This study also demonstrates the importance of going beyond traditional model organism research when trying to answer broad biological questions, and the potential insights further research on Ichthyosporean systems might reveal. "Ichthyosporean development displays remarkable diversity," said Dudin. "On one hand, several species exhibit developmental patterns similar to those of early insect embryos, featuring multinucleated stages and synchronised cellularisation. On the other hand, C. perkinsii undergoes cleavage division, symmetry breaking, and forms multicellular colonies with distinct cell types, similar to the 'canonical view' of early animal embryos. This diversity not only helps in understanding the path to animals but also offers a fascinating opportunity for comparative embryology outside of animals, which is, in itself, very exciting."

The project's inherent interdisciplinarity served not only as a good testbed for this type of collaborative research but also for the unique postdoctoral training afforded at EMBL. "Hiral's project nicely illustrates the virtue of the EIPOD programme: a truly interdisciplinary project, bundling innovative biology with advanced methods, all contributing to a truly spectacular personal development," said Schwab. "We (as mentors) witnessed the birth of a strong scientist, and this is really rewarding!"

The Dey, Dudin, and Schwab groups are currently also collaborating on the PlanExM project, part of the TREC expedition an EMBL-led initiative to explore and sample the biodiversity along European coasts. PlanExM aims to apply expansion microscopy to study the ultrastructural diversity of marine protists directly in environmental samples. "The project grew out of the realisation that U-ExM is going to be a game-changer for protistology and marine microbiology," said Dey. With this project, as well as others currently underway, the research team hopes to shed further light on the diversity of life on Earth and the evolution of the fundamental biological processes.

Source:

Journal reference:

Shah, H., et al. (2024). Life-cycle-coupled evolution of mitosis in close relatives of animals.Nature. doi.org/10.1038/s41586-024-07430-z.

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Study explores how different modes of cell division evolved in close relatives of fungi and animals - News-Medical.Net

Cell Biology

Solving the Wnt nuclear puzzle – Nature.com

Authors and Affiliations

Molecular Biology and Biochemistry, Simon Fraser University, Vancouver, British Columbia, Canada

Esther M. Verheyen

Centre for Cell Biology, Development, and Disease, Simon Fraser University, Vancouver, British Columbia, Canada

Esther M. Verheyen

Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Cara J. Gottardi

Department of Cell and Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Cara J. Gottardi

Correspondence to Esther M. Verheyen or Cara J. Gottardi.

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Solving the Wnt nuclear puzzle - Nature.com

Cell Biology

Prof. Jay Shendure Joins Somite Therapeutics as Scientific Co-founder – BioSpace

[[To comply with academic institution guidelines, the founders' academic affiliations and roles are listed only at the end of the statement.]]

BOSTON, May 21, 2024 /PRNewswire/ -- Somite Therapeutics, a tech-bio company harnessing big data and AI to pioneer novel cell replacement therapies, is thrilled to announce the addition of Prof. Jay Shendure as its newest Scientific Co-Founder.

Prof. Shendure, an HHMI Investigator and world leader in single-cell and functional genomic assays, has pushed the envelope on the scale of analyses that are possible today. He has developed massively parallel measurement approaches that solve open problems in biology and has increased the throughput of digital twin embryos by several orders of magnitude.

His addition to the team will help Somite advance its AI platform, AlphaStem, to develop cell replacement therapies for diseases such as diabetes, obesity, and muscular dystrophies.

"Our plan is to generate massive amounts of data to lay the foundation of our AI/ML platform, Alphastem," commented Dr. Micha Breakstone, Co-founder and CEO of Somite. "Prof. Shendure's addition marks a pivotal moment for our company as we continue to innovate and push the boundaries of what is possible in cell therapy."

About Prof. Jay Shendure

Jay Shendure, M.D., Ph.D. is an Investigator of the Howard Hughes Medical Institute, a Professor of Genome Sciences at the University of Washington, and Scientific Director of the Seattle Hub for Synthetic Biology (Allen-CZI-UW), the Allen Discovery Center for Cell Lineage Tracing, and the Brotman Baty Institute for Precision Medicine. His lab is known for the development and application of genomic technologies to outstanding challenges in genetics, molecular biology and developmental biology. Dr. Shendure is the recipient of the Curt Stern Award from the American Society of Human Genetics, the Richard Lounsbery Award from the National Academy of Sciences and the Mendel Award from the European Society of Human Genetics. He is also an elected member of the American Association for the Advancement of Science and the National Academy of Sciences. He received his MD and PhD degrees from Harvard Medical School.

About Somite

Somite.ai is a venture-backed company aiming to become the OpenAI of stem cell biology, developing AI foundation models to produce human tissue for cell therapies at scale for diseases such as diabetes, obesity, and muscular dystrophies. Somite's AI platform, AlphaStem, fuels a virtuous cycle: It enables new cell therapies, generating massive data that further improve the platform, empowering even faster therapy creation with broader applications.

Incorporated in Oct. 2023, Somite.ai has raised $5.3m to date.

Somite Management Team:

Scientific Co-founders:

Media Contact: media-relations@somite.ai Website: http://www.somite.ai

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Prof. Jay Shendure Joins Somite Therapeutics as Scientific Co-founder - BioSpace

Cell Biology

One essential step for a germ cell, one giant leap for the future of reproductive medicine – EurekAlert

image:

Image inspired by NASA's Apollo Program, representing the successfulin vitrogerm cell differentiation from TFAP2C-EGFP +ve human primordial germ cell-like cells (hPGCLCs; labeled in green) to DAZL-tdTomato +ve human mitotic pro-spermatogonia (labeled in red).

Credit: WPI-ASHBi/Kyoto University

KYOTO, Japan May 20, 2024

Infertility affects approximately 1 in 6 people in their lifetime worldwide according to the World Health Organization (WHO). Infertility as defined by the American Society for Reproductive Medicine (ASRM) is a disease, condition, or status characterized by the inability to achieve a successful pregnancy based on a patients medical, sexual, and reproductive history, age, physical findings, diagnostic testing, or any combination of those factors or requiring medical intervention such as the use of mature donor gametes to achieve a successful pregnancy either as an individual or with a partner. Although assisted reproductive technologies (ARTs), such as in vitro fertilization (IVF), have had a tremendous impact in treating certain forms of infertility not all forms of infertility (as defined by the ASRM) can be targeted with existing strategies.

Recently, one powerful technology has emerged known as human in vitro gametogenesis (IVG) using pluripotent stem cells (PSCs) such as induced pluripotent stem cells (iPSCs) from patients, to generate human germ cells with the capacity to potentially give rise to mature gametes in culture, offering a gateway to treating all form of infertility independent of gender. Nevertheless, human IVG research still remains in its infancy, with the current goal being to reconstitute the complete process of human gametogenesis. To date, one major challenge has been to recapitulate in the founder population of germ cells, or the human primordial germ cells (hPGCs), a hallmark event known as epigenetic reprogramming in which the inherited parental memory of cells, present on its DNA, is reset/erased that is required for proper germ cell differentiation.

Now, in a study published in Nature, researchers at the Institute for the Advanced Study of Human Biology (WPI-ASHBi) in Kyoto University, led by Dr. Mitinori Saitou, identify robust culture conditions necessary to drive epigenetic reprogramming and germ cell differentiation into precursors of mature gametes, the mitotic pro-spermatogonia and pro-oogonia with the capacity for extensive amplification, achieving a new milestone for human IVG research.

Previous work from Saitous team and other groups were successful in generating so-called human primordial germ cell-like cells (hPGCLCs) from PSCs in vitro, which recapitulated several fundamental features of hPGC, including the capacity to propagate. However, these hPGCLCs were unable to undergo epigenetic reprogramming and differentiation. Although such limitations could be bypassed by aggregating hPGCLCs with mouse embryonic (non-germinal) gonadal cells to mimic the microenvironment of the testis/ovary, thereby effectively reconstitute the tissue(s). However, this process is highly inefficient (with approximately only 1/10th of cells differentiating). Furthermore, the introduction of non-human cells is neither ideal nor practical from a clinical application perspective. Therefore, in order to achieve the ultimate goal of human IVG research, it is essential to identify the minimal culture conditions necessary to generate mature human gametes.

In their new study, Saitou and colleagues conducted a cell culture-based screen to identify potential signaling molecules required to drive epigenetic reprogramming and differentiation of hPGCLCs into mitotic pro-spermatogonia and oogonia. Surprisingly, the authors found that the well-established developmental signaling molecule, bone morphogenetic protein (BMP), played a crucial role in this reprogramming and differentiation process of hPGCLCs.

Indeed, considering that BMP signaling already has an established role in germ cell specification, it was highly unexpected that it also drives hPGCLC epigenetic reprogramming comments Saitou.

Remarkably, these hPGCLC-derived mitotic pro-spermatogonia/oogonia not only displayed similarities in gene expression and epigenetic profiles to that of actual hPGC differentiation in our bodies, but also underwent extensive amplification (over 10 billion-fold). Our approach enables near-indefinite amplification of mitotic pro-spermatogonia and oogonia in culture and we now also have the ability to store and re-expand these cells as needed says Saitou.

The authors also revealed the potential mechanisms of how BMP signaling may be leading to epigenetic reprogramming and hPGCLC differentiation. BMP (signaling) appears to be attenuating the MAPK/ERK (mitogen-activated protein kinase/extracellular-regulated kinase) signaling pathway and both the de novo and maintenance activities of DNMT (DNA methyltransferase), but further investigation will be necessary to determine the precise mechanism and whether this is direct or indirect, explains Saitou.

Our study represents not only a fundamental advance in our understanding of human biology and the principles behind epigenetic reprogramming in humans but also a true milestone in human IVG research says Saitou.

Saitou comments, although many challenges remain and the path will certainly be long, especially when considering the ethical, legal, and social implications associated with the clinical application of human IVG, nevertheless, we have now made one significant leap forward towards the potential translation of IVG into reproductive medicine.

These findings were published in Nature on May 20th 2024.

###

By

Spyros Goulas, PhD

Scientific Advisor

Institute for the Advanced Study of Human Biology (ASHBi)/Kyoto University

Email: goulas.spyros.3n@kyoto-u.ac.jp

Lead Principal Investigator

Mitinori Saitou, MD PhD

Institute for the Advanced Study of Human Biology (ASHBi)/Kyoto University

Email: saitou@anat2.med.kyoto-u.ac.jp

###

About Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University

What key biological traits make us human, and how can knowing these lead us to better cures for disease?ASHBi investigates the core concepts of human biology with a particular focus on genome regulation and disease modeling, creating a foundation of knowledge for developing innovative and unique human-centric therapies.

About the World Premier International Research Center Initiative (WPI)

The WPI programwas launched in 2007 by Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS).

Experimental study

Cells

In Vitro Reconstitution of Epigenetic Reprogramming in the Human Germ Line.

20-May-2024

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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One essential step for a germ cell, one giant leap for the future of reproductive medicine - EurekAlert

Cell Biology

May: academy-medical-sciences | News and features – University of Bristol

Two Bristol academics, Professors Eugenia Piddini and Gene Feder OBE, have been elected to the Academy of Medical Sciences respected and influential Fellowship. They join 58 exceptional biomedical and health scientists selected for their exceptional contributions to the advancement of medical science.

The new Fellows, announced on Tuesday 21 May, have been recognised for their remarkable contributions to advancing biomedical and health sciences, groundbreaking research discoveries and translating developments into benefits for patients and wider society.

Awardees join an esteemed Fellowship of over 1,400 researchers who are at the heart of the Academy's work, which includes nurturing the next generation of researchers and shaping research and health policy in the UK and worldwide. The expertise of Fellows elected this year spans a wide range of clinical and non-clinical disciplines, from midwifery to cancer stem cell biology.

Eugenia Piddini, Professor of Cell Biology in the School of Cellular and Molecular Medicine, is conducting innovative work to identify cell competition-based strategies to gain control over tissue colonisation, its impact in tissue colonisation in regenerative medicine and to prevent tumour expansion in cancer.

A cell and developmental biologist,Eugenia is known for her seminal work in the field of cell competition the mechanism of tissue quality control that removes damaged cells from tissues. Eugenias discoveries have helped widen the scope of cell competition in terms of physiological relevance and potential therapeutic impact. Recently, Eugenias group demonstrated that cell competition acts in adult tissues. There it can potentially slow down the onset of disease/ageing by eliminating damaged cells.

Eugenias team has also shown that tumour cells kill surrounding normal cells via cell competition to free space for their own growth. Their work has identified many mechanisms and signals that cells use to compete. By explaining the mechanisms that cells use to compete the Piddini group aims to identify cell competition-based strategies to gain control over tissue colonisation.

In recognition of her work Eugenia, who is also School Research Director, was awarded the British Society for Cell Biology Hooke Medal in 2019 and in 2023, was elected as a Member of the European Molecular Biology Organisation.

Gene Feder, is a GP and Professor of Primary Care at Bristols Centre for Academic Primary Care, Bristol Medical School and Director of VISION, a UK Prevention Research Partnership (UKPRP) consortium.

Professor Feder leads ground-breaking national and international research on domestic violence and abuse (DVA) from epidemiology to health care response. He is the architect of IRIS, a national DVA programme for general practice, and co-founded IRISi, a social enterprise implementing IRIS nationally. He has extended his research globally through EU and Medical Research Council grants, and co-leadership of HERA, a National Institute for Health and Care Research (NIHR) Global Health Group in collaboration with researchers in Brazil, Nepal Sri Lanka, and the occupied Palestinian territories (oPT).

Committed to developing and evaluating effective and compassionate health care, Professor Feder has championed the use of randomised controlled trials to test improvements in general practice care of patients with heart and respiratory conditions, and robust methods to develop and implement clinical guidelines that make a difference to patients. He extended epidemiological, trial and meta-analytic methods to research on gender-based violence, combining quantitative and qualitive data to evaluate interventions, collaborating with statisticians, epidemiologists, economists, and social scientists. He has chaired four NICE guidelines and the World Health Organisation (WHO) intimate partner and sexual violence guideline development group.

In 2012, he co-founded the Foundation for Family Medicine in Palestine, which aims to support universal health coverage throughout the occupied Palestinian Territories based on effective, efficient and high-quality primary care. In 2016, Professor Feder was awarded an OBE for services to health care and survivors of domestic violence. In 2022, Gene was appointed Director of VISION, a five-year UKPRP inter-disciplinary consortium researching the intersection of violence and health to reduce and mitigate the effects of violence through better measurement and analysis of health care, police, criminal justice, and voluntary sector data. He is an expert advisor to UK Government and WHO.

Professor Andrew Morris PMedSci, President of the Academy of Medical Sciences, said: It is an honour to welcome these brilliant minds to our Fellowship. Our new Fellows lead pioneering work in biomedical research and are driving remarkable improvements in healthcare. We look forward to working with them, and learning from them, in our quest to foster an open and progressive research environment that improves the health of people everywhere through excellence in medical science.

This year's cohort marks a significant milestone in the Academy's efforts to promote equality, diversity and inclusion (EDI) within its Fellowship election. Among the new Fellows, 41 per cent are women, the highest percentage ever elected. Additionally, Black, Asian and minority ethnic representation is 29 per cent, an 11 per cent increase from the previous year. The new Fellows hold positions at institutions across the UK, including in Edinburgh, Birmingham, Liverpool, Manchester, Sheffield, Nottingham and York.

Professor Morris added: It is also welcoming to note that this year's cohort is our most diverse yet, in terms of gender, ethnicity and geography. While this progress is encouraging, we recognise that there is still much work to be done to truly diversify our Fellowship. We remain committed to our EDI goals and will continue to take meaningful steps to ensure our Fellowship reflects the rich diversity of the society we serve."

The new Fellows will be formally admitted to the Academy at a ceremony on Wednesday 18 September 2024.

The Academy of Medical Sciences is the independent, expert body representing the diversity of medical science in the UK. Its mission is to advance biomedical and health research and its translation into benefits for society. The Academy's elected Fellows are the most influential scientists in the UK and worldwide, drawn from the NHS, academia, industry and the public service.

About the Academy of Medical SciencesThe Academy of Medical Sciences is the independent, expert voice of biomedical and health research in the UK. Our Fellowship comprises the most influential scientists in the UK and worldwide, drawn from the NHS, academia, industry, and the public service. Our mission is to improve the health of people everywhere by creating an open and progressive research sector. We do this by working with patients and the public to influence policy and biomedical practice, strengthening UK biomedical and health research, supporting the next generation of researchers through funding and career development opportunities, and working with partners globally.

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May: academy-medical-sciences | News and features - University of Bristol

Cell Biology

Universal tool for tracking cell-to-cell interactions – ASBMB Today

One of the fundamental goals of basic biology is understanding how diverse cell types work in concert to form tissues, organs, and organ systems. Recent efforts to catalog the different cell types in every tissue in our bodies are a step in the right direction, but only one piece of the puzzle. The great mystery of how those cells communicate with one another remains unsolved.

The LIPSTIC technology can track the physical interactions between cells, such as a dendritic cell activating T cells.

Now, a new paper in Nature describes uLIPSTIC, a tool capable of laying the groundwork for a dynamic map tracking the physical interactions between different cellsthe elusive cellular interactome. The authors have been perfecting the technology since 2018 and the latest iteration can in principle allow researchers to directly observe any cell-to-cell interaction in vivo.

With uLIPSTIC we can ask how cells work together, how they communicate, and what messages they transfer, says Rockefellers Gabriel D. Victora. Thats where biology resides.

Ever since single-cell mRNA sequencing came into its own, researchers have been scrambling to connect the dots and explain how diverse cells unite to form tissue. Several methods of cataloging cell-to-cell interactions have already emerged, but all have considerable shortcomings. Early efforts that involved direct observation under a microscope failed to retrieve interacting cells for further analysis; subsequent attempts leaned on advanced imaging techniques that intuit how cells might interact based on their structure and proximity to other cells. No approach captured true physical interactions and signal exchange between cell membranes.

Enter LIPSTIC, an innovative approach from the Victora lab that involved labeling cellular structures that touch when two cells make fleeting, kiss-and-run contact before parting ways. The labels ensured that, if one cell kissed another, it would leave a mark akin to a lipstick, enabling easy identification and quantification of physical interactions between cells.

Originally, the platform had narrow applications. Victora and colleagues designed LIPSTIC to record a very specific kind of cell-to-cell interaction between T cells and B cells, a major focus of their lab. Other researchers, however, began clamoring for a version of LIPSTIC that would work on other cellular interactions too. We could have tailored a LIPSTIC for every type of interaction, Victora says. But why not try to make a universal version, instead?

In the original version of LIPSTIC, a donor cell uses an enzyme borrowed from bacteria to place a labeled peptide tag onto the surface of an acceptor cell upon contactthe biochemical equivalent of applying lipstick to one cell and looking for a kiss print on another. That method required knowing exactly how the kiss would occur, identifying molecules the donor cell uses to interact with recipient cells and painstakingly forcing the tags onto those molecules. But over time the team discovered that dousing the cells with a high volume of enzyme and its target would ensure that any interaction that one cell had with another cell would be tracked just as efficiently.

If you cram partner cells with enough enzyme and target, you can make any any cell pair capable of LISPTIC labeling without needing to know in advance what molecules these cells will use for their interaction, Victora says.

The result was uLIPSTIC, a universal platform not bound by foreknowledge of molecules, ligands, or receptors. Scientists can now theoretically smear uLIPSTIC on any cell, without preconceived notions of how it would interact with its environment, and observe physical cell-to-cell interactions. To demonstrate the power of the platform, the team showed that uLIPSTIC could expand beyond LIPSTICs narrow repertoire of B cells and T cells to track how dendritic cells kickstart the bodys immune response against tumors and food allergens.

The reception to uLIPSTIC has been great, says Sandra Nakandakari-Higa, a PhD student in the Victora lab and lead author on the paper. Were already getting a lot of inquiries from other labs about how they can adapt our system to their models.

The team hopes to eventually use uLIPSTIC to discover the receptor-ligand pairs key to cellular interactions, in an effort to better understand how cells unite into tissue at the molecular level. Eventually, the team envisions uLIPSTIC as a key tool in the effort to generate comprehensive atlases describing how cells interact to form tissuea key to the long-awaited interactome.

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Universal tool for tracking cell-to-cell interactions - ASBMB Today

Cell Biology

Close Encounters of Skin and Nerve Cells – The Scientist

A tickly itch, a painful scratch, or the feeling of a refreshing breezethe skin is teaming with nerve endings that drive these sensations. Scientists are getting into the epidermis to explore how skin and nerve cells interact.

Peering through a microscope at skin tissue, researchers struggle to tease apart the intricate connections occurring inside tight bundles of skin and nerve cells.1 However, recent advances in microscopy have helped solve this intractable problem. Published in eLife, Nurcan eyler, a neurologist at the University of Wrzburg, and her colleagues used emerging imaging techniques to discover that nerve fibers not only weave around skin cells but also pass through them.2 The findings intimate a route by which skin cells transmit sensory signals to the nervous system.

The skin is basically the window to the outside, said Kathryn Albers, a neuroscientist at the University of Pittsburgh who was not involved with the work but reviewed the study. Despite this, scientists have long overlooked the role skin cells play in nerve stimulation. eyler hopes that their findings will open new doors for research. I think were at the beginning of changing minds, she said.

A chance discovery made by Christoph Erbacher, then a doctoral student in eylers laboratory, set the project in motion. He had started working on his PhD thesis on a completely different topic, eyler said. However, when Erbacher looked at skin tissue under the microscope, he noticed that nerve fibers did not just grow around skin cells but, to the whole teams surprise, tunneled straight through them. Eager to inspect these interactions in closer detail, the team turned to state-of-the-art imaging strategies that zoom deep inside cells to bring fine structures into view.

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Structured illumination microscopy, a technique that takes multiple snapshots of a sample under different patterns of light, allowed eyler and her team to acquire super-resolution images of skin tissue. With the help of fluorescent antibodies that bind specifically to nerves, they located nerve tunnels passing through skin cells. Then, to capture the cells interior architecture, they used electron microscopy.3 The combination of the two strategies, called correlative light and electron microscopy (CLEM), allowed the researchers to see which architectural details corresponded to the fluorescently-stained nerve fibers.4

A single snapshot of a cell can only reveal so much. By imaging several layers in a sliver of tissue,the researchers could determine whether a nerve fiber tunneled through a cell rather than over or under it. They scrolled through cross-sections of the cell, starting at the base and moving up. All of a sudden, the fiber appears, and you can very clearly see youre in the middle of the cell, eyler said.

Examining the close-up architectural details afforded by CLEM, the researchers noticed that the tunneling fiber, as thin as one micrometer in width, did not puncture the skin cell membrane and poke into the cytoplasm, like a needle piercing through flesh. Rather, the membrane ensheathes the fiber, like rubber insulation around electrical wires.

Researchers captured nerve fibers (green) tunnelling through skin cells (magenta) using cutting-edge microscopy. Scale bar = 5m

Christoph Erbacher

With a detailed view of skin-nerve connections, the researchers explored whether proteins responsible for transmitting signals accumulate on these tunneling fibers. Using a flurry of fluorescent antibodies to search for such a protein, they found that connexin 43, a protein that normally participates in communication between skin cells, decorated the nerve fibers.5 Connexin 43 aggregates in a ring to generate pores in the cell membrane that allow entry of chemical signals such as calcium ions.6 eylers team also found that the calcium ion level spiked inside the cells when the nerve fibers tunneled through, which suggested that the two cell types communicate.

What started out as a chance observation may have implications for healthcare down the road. This skin-nerve cell link could inform research on nervous system disorders that affect the skin. For example, small fiber neuropathy causes a chronic, persistent burning pain on the skin, and eyler hopes that future studies will reveal whether nerve tunnels play a role in the condition.7 Currently, the few treatment options that exist target the nerves directly, but researchers may one day develop therapies that target the skin cells instead.

Before that can happen, scientists must first scratch deeper to unravel the biology of these nerve tunnels. Albers would like to know how these tunnels entwine with skin cells as they migrate from the base layer to the skin surface. She also wondered if nerve fibers tunnel into other cell types found in skin tissue, such as immune cells, and what that crosstalk between cell types might achieve.

No one tissue exists alone; everything communicates at some level, said Albers.

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Close Encounters of Skin and Nerve Cells - The Scientist

Cell Biology

OrthoID: Decoding Cellular Conversations with Cutting-Edge Technology – yTech

Summary: OrthoID is a novel strategy developed by an interdisciplinary research team to enhance our understanding of organelle communication within cells. It surmounts issues inherent in traditional methodologies and brings forth new levels of clarity to the study of cellular processes related to health and disease.

Within the realm of cellular biology, the nuanced dialogue between organelles like mitochondria and the endoplasmic reticulum (ER) is critical for maintaining cell health. Disruptions in this dialogue have implications in a host of diseases, making it imperative to understand it in detail. Innovatively engineered, OrthoID has been meticulously crafted to offer us deeper insights into organelle communication.

OrthoID differentiates itself from previous methods by using a synthetic binding pair in conjunction with the classic streptavidin-biotin system. This dual binding scheme unveils previously hidden facets of organelle interaction, enabling researchers to capture a broader array of mediator proteins. The technique has already borne fruit, uncovering novel proteins like LRC59 and illuminating their specific functions within the ER-mitochondria contact sites.

The flexibility of OrthoID is one of its many innovations, allowing scientists to customize their approach to studying various organelle interactions. This adaptability was emphasized by Professor Kimoon Kim of POSTECH, who noted the technologys modular nature that could extend beyond ER-mitochondrial studies. Meanwhile, Professor Kyeng Min Park from Daegu Catholic University School of Medicine highlighted its role as a versatile research instrument with promising applications in both understanding and treating diseases.

Overall, OrthoID is forging a path towards a transformative comprehension of cell mechanics, directly impacting future biomedical research and therapy development. The techniques unique perspective on the protein players in organelle communication is reshaping how scientists approach the intricate cellular landscape, bringing us one step closer to unraveling the mysteries of cellular life.

Industry Overview

The biotechnology and pharmaceutical industry is increasingly focusing on cellular biology as a fundamental aspect of understanding disease and developing new therapies. Organelle communication within cells is particularly pertinent to a range of conditions, including neurodegenerative diseases, cancer, and diabetes. The market for cell biology reagents and technologies is on a persistent growth trajectory, fueled by expanding research in cell and molecular biology. Market forecasts suggest that the global market for these technologies, driven by the need for more precise diagnostic tools and effective therapeutic options, is expected to experience significant growth over the next several years.

Market Forecasts

According to industry forecasts, one can expect the market for cell biology reagents and instruments to reach billions of dollars by the end of the decade. North America and Europe are leading this growth, with Asia-Pacific regions showing the highest growth rates due to increasing investments in biotechnology and healthcare infrastructure.

Industry Issues

Despite the anticipated growth, the industry faces several issues. High costs and technical complexities of advanced technologies can pose barriers to entry for smaller research institutions. Intellectual property rights, stringent regulatory frameworks, and ethical considerations surrounding biomedical research are additional challenges that impact industry dynamics. Furthermore, the reproducibility crisis in biological sciences, referring to the difficulty in replicating and validating research findings, underscores the need for reliable technologies like OrthoID.

OrthoIDs Role in the Industry

The development of OrthoID signifies a substantial advancement in the field. It provides a more discerning and versatile tool for the dissection of organelle communication pathways. As diseases often affect or are affected by cellular processes, mastering the intricacies of cell function with technologies like OrthoID can lead to the discovery of novel therapeutic targets. In the near future, this could facilitate the development of treatments that are more targeted and effective.

With continued research and development, medical scientists and researchers can leverage OrthoIDs detailed insights into organelle communication to overcome diseases that have remained enigmatic thus far. In the ever-evolving landscape of biotechnology, products such as OrthoID that provide novel means of understanding biological systems are invaluable.

For more information on the latest advancements and trends within the biotechnology industry, consider visiting reputable sources like the Nature Publishing Group or the World Health Organization (WHO), which can provide up-to-date news and comprehensive reports.

Micha Rogucki is a pioneering figure in the field of renewable energy, particularly known for his work on solar power innovations. His research and development efforts have significantly advanced solar panel efficiency and sustainability. Roguckis commitment to green energy solutions is also evident in his advocacy for integrating renewable sources into national power grids. His groundbreaking work not only contributes to the scientific community but also plays a crucial role in promoting environmental sustainability and energy independence. Roguckis influence extends beyond academia, impacting industry practices and public policy regarding renewable energy.

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OrthoID: Decoding Cellular Conversations with Cutting-Edge Technology - yTech