Category Archives: Cell Biology

Cell Biology

Better Than MDA: PTA Whole Genome Amplification Has More Info, Fewer Errors – BioSpace

BioSkryb has developed a more robust technology for whole genome sequencing that accurately and uniformly captures more than 95% of the genomes of single cells.

Dubbed primary template-directed amplification (PTA), this is the foundational technology behind BioSkrybs ResolveDNA kits.

PTA lets researchers see genetic changes that other WGA technologies lose, Chuck Gawad, M.D., Ph.D., co-founder and director of BioSkryb, told BioSpace.

Its all based around resolution, so ResolveDNA is analogous to providing a better microscope but for the genome, said co-founder and CEO Jay West, Ph.D.

Kits contain the core technology (including proprietary nucleotides) and a product solution (the enzymes and reagents) to help researchers amplify the genome of samples as small as a single cell to prepare and analyze the data, looking at the whole genome of a species. Cell barcodes also can be attached to the amplification products for pooling and downstream analysis.

The companys initial focus is around oncology.

Theres a lot of the genetic diversity in tumors that isnt captured by standard sequencing, so researchers havent seen enormous utility from sequencing, Gawad said.

He began tackling the problem as a post-doc at Stanford University and continued the work in his own lab at St. Jude Childrens Research Hospital, where he finally teased out a solution. It was a simple idea, but became quite powerful.

As Gawad and colleagues explained in a recent research paper, Accurate Genomic Variant Detection in Single Cells with Primary Template-Directed Amplification, PTA takes advantage of the processivity, strong strand displacement activity, and low-error rate of phi29 polymerase used in (multiple displacement amplification) MDA. Howeverexonuclease-resistant terminators are incorporated into the reaction, creating small double-stranded amplification products that undergo limited subsequent amplification. This transforms the reaction from exponential into a quasilinear process, with more of the amplification occurring from the primary template.

This approach allowed DNA proportions to be maintained after amplification and the genome to be copied evenly, thus reducing artifacts, Gawad said. Were capturing more information from the genome, with fewer errors.

Importantly, PTA technology can be dropped into labs without affecting workflow. It takes about an hour of hands-on time and requires only a few steps, he added.

Analysis is performed on Trailblazer, BioSkrybs cloud-based bioinformatics platform.

Before BioSkryb launched the ResolveDNA and Trailblazer technology, the company took it to key opinion leaders and major laboratories that are well-versed in WGA.

They were overwhelmingly positive, Gawad said. When comparing PTA results to their prior WGA data, They found that a lot of artefacts in the data e disappeared and gaps were filled in, so they have a new level of detail, which has led to novel insights.

ResolveDNA is commercialized, but the company is still in its innovation phase, West said. Were releasing products for research use only. We have a long-term mission to improve patient outcomes, but first we have to move into the market and have clinical validation of the product.

Eventually, West envisions clinical applications, such as enabling physicians to select therapies based on the genomics of tumor cells.

Cancer is a tough disease, West said. Some tumor cells dont respond to a given therapy. They evade and repopulate, causing a relapse. When that happens, the genetic composition of the tumor has changed. Thats hard to assess using standard technology.

PTA may allow those changes to be identified and annotated for better-focused therapies.

BioSkryb developed DMEM, a tool to map genome-wide interactions of mutagens, as part of its mission to develop new applications for WGA. As Gawad explained, DMEM lets researchers measure the magnitude, genomic locations and nucleotide context of ENU-induced mutations in living human cells. It offers base pair resolution for living single cells, making it valuable in measuring off-target actions for drug candidates.

This is a marked contrast to the widely-used Ames test. That test, developed in the 1970s, tests chemicals against a particular strain of Salmonella typhimurium to determine toxicity.

How that is related to human genetics is unknown, but it probably only partially captures the effects of mutagens in human cells, Gawad said.

As West said, We are passionate about translational science asking biological questions that have real clinical impact. Single-cell genomics applications include the ability to perform single-cell evaluations of biopsies, including:

Other applications include:

To expand applications, BioSkryb recently announced a grant program to fund two researchers up to $20,000 each to demonstrate that their research can fuel new discoveries in single-cell genomics and help improve human health. Applications will be accepted through January 29, 2021 and awarded March 1 at The Advances in Genome Biology and Technology (AGBT) 2021 General Meeting.

At BioSkryb, West continued, Were focused on supporting the research market broadly. ResolveDNA can be used for high-throughput, parallel reactions in microfluidic devices or emulsions. To that end, the company is working to increase throughput beyond its current 24 & 96-reaction/cell format. It also may combine transcriptomic amplification and analysis to its genomic model, allowing researchers to gain insights into the relationships among cell state, genotype, and cellular phenotype.

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Better Than MDA: PTA Whole Genome Amplification Has More Info, Fewer Errors - BioSpace

Cell Biology

Top 15 Biotech Companies Shaking up the Scene in… – Labiotech.eu

Cambridge has a large biotech scene that is starting to rival that of its US namesake. Here are the top 15 biotech companies in Cambridge you should know about.

Cambridge is a small but vibrant city that is well known for its university and for being a center of excellence for life sciences and health-related research. The Wellcome Sanger Institute, where part of the human genome was sequenced, is on its outskirts, next to the European Bioinformatics Institute. There are also a number of world-class research institutes in the vicinity including Addenbrookes Hospital.

While the city has historically had more of an academic research focus, in recent years it has become a major biotech and pharma hub. Antibody development is one of the strengths of the city thanks to the legacy of Cambridge Antibody Technologies, which pioneered the technology of phage display and developed Humira, the worlds best-selling drug. Newer therapeutic areas are also represented, such as RNA silencing, cell and gene therapies, and the microbiome, as well as companies using artificial intelligence to improve drug discovery.

As there are so many excellent companies in the region, it was hard to choose only 15. After consultation with local experts, here are our choices in no particular order.

Founded: 2010

Kymab is one of several Cambridge companies focusing on antibody therapies, such as F-Star Therapeutics or Crescendo Biologics. The company was spun out of the Wellcome Sanger Institute to rapidly develop bispecific antibodies using genetically engineered mice.

Kymab has eight products in its pipeline targeting cancer, hemophilia, and several immune disorders. Its most advanced candidate is a treatment for atopic dermatitis that recently reported successful results from a phase II trial.

The company has raised almost 200M to date. It has an ongoing patent dispute with US biotech Regeneron; in June, the US patent office rejected a fifth request by Regeneron to invalidate Kymabs US patents and the UK Supreme Court ruled in favor of Kymab.

Founded: 2009

Founded by Nobel prize winner and Cambridge professor Sir Greg Winter, Bicycle Therapeutics develops a new class of drugs called bicyclic peptides, which blend the ability of traditional antibodies to hunt normally undruggable proteins with the manufacturing ease of small molecule drugs.

Its technology caught the eye of AstraZeneca, which struck a 1B deal to tackle respiratory, cardiovascular, and metabolic diseases in 2016. Two years later, the companys first peptide began clinical trials to treat solid tumors that express high levels of a protein called metalloproteinase.

In 2019, the company listed on the Nasdaq stock exchange in a downsized IPO of 50M. This year the company made a deal with Genentech worth up to 1.6B to develop novel cancer immunotherapies.

Founded: 2011

Mission Therapeutics is developing small molecule drugs to inhibit deubiquitylating enzymes, which regulate the degradation of proteins within the cells. These enzymes are involved in a wide range of conditions including mitochondrial diseases, kidney injury, pulmonary fibrosis, and Parkinsons disease.

Mission Therapeutics raised 75M in one of the biggest rounds of European biotech back in 2016. This year, it raised an additional 12.4M and struck a drug development deal with Pfizer. The company currently has four programs in its pipeline, four of them in preclinical development.

Founded: 2013

Another spin-off from the Wellcome Sanger Institute, Congenica uses genomic analysis to assist in the diagnosis of rare diseases. The company has partnerships with many UK hospitals for genomic diagnostics and works with UCB in Belgium in drug discovery programs.

Congenica has developed a clinical genome analysis platform called Sapientia that uses machine learning to produce diagnostic reports from genomic data collected in hospitals and other research institutions around the world.

Last year, the company raised funds to support the use of its rare disease diagnostics platform by the newly formed NHS Genomic Medicine Service. This was topped up with a 41M Series C last month to drive the companys international expansion.

Founded: 2016

Artios Pharma is developing drugs that inhibit an enzyme called DNA polymerase theta, which plays a role in multiple DNA repair processes. The levels of this enzyme are typically higher in several types of tumors, including breast, ovarian and lung cancers, than in healthy tissue.

The company had an oversubscribed 73M Series B round in 2018. Earlier this month, the company signed a 5.7B megadeal with Merck KGaA to develop DNA damage repair cancer therapeutics. Its first clinical trial in humans is planned for 2021.

Founded: 2014

Healx uses artificial intelligence to analyze extensive medical research data with the goal of repurposing existing drugs to treat rare diseases. The companys most advanced program, a drug repurposed for fragile X syndrome, took less than two years to reach clinical trials instead of the normal five-to-seven years this process usually takes.

The company raised a 50.8M Series B round in October 2019. Shortly after, Healx started the Rare Treatment Accelerator program, allowing patient advocacy groups a chance to work with the company to find new treatments for rare diseases.

Healx has a mission to advance 100 rare disease treatments towards the clinic by 2025. Since the start of the pandemic, the company has been using its technology to search for treatments for Covid-19.

Founded: 2019

Cyted is applying artificial intelligence to the development of diagnostics. The company is collaborating with Medtronic to develop an early detection esophageal cancer test. Medtronics technology is based on a device that can be swallowed like a pill, invented by one of Cyted founders before starting the company.

Cyted raised 9.6M in February this year and acquired Pathognomics, a provider of digital pathology and clinical diagnostic laboratory services that will allow the company to scale up and roll out its diagnostic services.

Founded: 2015

Storm Therapeutics was spun out of the University of Cambridge to treat cancer and other diseases using a technology to modulate RNA-modifying enzymes, such as RNA methyltransferase.

The company raised 34M in Series A funding in 2019. Its most advanced drug candidate is now ready to enter clinical trials as a treatment for leukemia.

There has been increasing interest in companies working in the RNA space since the first RNA interference therapy was approved in 2018 and the recent approval of the first Covid-19 vaccine using messenger RNA technology in the UK and Canada.

Founded: 2012

Cambridge Epigenetix was founded by Cambridge professor Sir Shankar Balasubramanian, who co-invented the technology behind next-generation sequencing now used by DNA sequencing giant Illumina.

Cambridge Epigenetix pioneered epigenetic tests for the early detection of cancer and other diseases. Its technology is able to reveal information about the activity of disease-related genes not available using genetic analysis alone. The company has raised approximately 50M to date.

Founded: 2016

Mogrify uses an algorithm to predict what chemicals are needed to convert any human cell type into another cell type.

The company raised a 14.5M Series A last year and signed a licensing agreement with genomic medicine company Sangamo earlier this year to help the US company scale up the production of off-the-shelf cell therapies for inflammatory and autoimmune diseases.

In October, Mogrify announced the launch of a platform that can model the epigenetic state of cells and provide important information on switches that can change cell biology.

Founded: 2016

Previously known as Elpis Biomed, Bit Bio was founded by neurosurgeon and cell therapy specialist Mark Kotter, who is also a Cambridge academic. The company is creating cell therapies through cellular reprogramming.

Bit Bios approach is to screen large datasets for cocktails of proteins that are needed to turn stem cells into the desired cell type. The company then genetically engineers the stem cells so that they switch on the production of these proteins when given an antibiotic.

The company has so far raised 44.4M to support the development of this technology.

Founded: 2015

Evonetix is working on a fast, scalable, high fidelity approach to DNA synthesis. The company is currently developing a DNA on a chip technology that will allow DNA to be made simultaneously at many different points on a silicon chip via electronic programming.

The company has so far raised approximately 36M. Earlier this year, Evonetix partnered with imec, a Dutch research and innovation hub active in the fields of nanoelectronics and digital technologies. This will increase the production of Evonetixs chips, enabling the platform to be manufactured at a commercial scale.

Founded: 2016

Microbiotica was established in 2016 as a spin-out from the Wellcome Sanger Institute. The company uses clinical data and detailed microbiome profiling to develop therapeutics and diagnostic biomarkers

In 2018, Microbiotica entered into a collaboration with Genentech worth up to 452M to develop microbiome-based treatments for inflammatory bowel disease. The company is also developing treatments for cancer and Clostridium difficile infections

In June, Microbiotica started a collaboration with Cancer Research UK and Cambridge University Hospitals NHS Foundation Trust to identify and develop combinations of microbiome therapeutics and biomarkers for cancer patients receiving immune checkpoint inhibitor therapy.

Founded: 2016

NodThera is targeting several inflammatory conditions affecting the liver, lungs, and bowels.These conditions involve excessive activation of a multi-protein complex called the NLRP3 inflammasome, which has received a lot of interest from big pharma over the past year. This complex regulates the release of two proinflammatory proteins that normally help the body to get rid of infection or heal tissue damage.

The company raised 48.7M in Series B funding in the summer. Its most advanced candidate is now in phase I clinical trials.

Founded: 2009

CN Bio Innovations develops human organ-on-a-chip technology for testing and developing therapies to treat human diseases. Having initially operated in stealth mode, the company is now selling products and services and vocal about it.

CN Bio works with academic bioengineering groups at MIT and Imperial College London and provides its technology to the US FDA. Last month, the company launched a commercial drug metabolism and safety toxicity testing service for researchers and companies to assess liver toxicity of various compounds.

Cover illustration by Anastasiia Slynko

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Top 15 Biotech Companies Shaking up the Scene in... - Labiotech.eu

Cell Biology

ONK Therapeutics Announces Three Exclusive Option License Agreements, Which Extend and Strengthen its Dual-Targeted NK Cell Therapy Pipeline -…

Dec. 17, 2020 08:30 UTC

GALWAY, Ireland, & SAN DIEGO, Calif.--(BUSINESS WIRE)-- ONK Therapeutics Ltd, an innovative natural killer (NK) cell therapy company, today announced that it has secured three new exclusive option license agreements which strengthen its off-the-shelf, dual-targeted natural killer (NK) cell therapy platform and extend its pre-clinical pipeline to four programs across both hematological and solid tumors.

The first option agreement, with Cellerant Therapeutics, gives exclusive rights to a humanized CLEC12A scFv binder. CLEC12A is strongly expressed by blasts in the majority of AML patients. The option to license has enabled ONK to expand its pre-clinical product portfolio, launching a fourth program (ONKT104). This dual-targeted approach combines the CLEC12A CAR with a TNF-related apoptosis-inducing ligand variant (TRAILv) targeting death receptor 4 (DR4).

While expressed on leukemic stem cells, CLEC12A is absent from normal hematopoietic stem cells and we thus expect that our dual-targeted NK cell therapy approach should enable safe targeting, with a reduced risk of prolonged aplasia in AML, said Prof Michael ODwyer MD, ONK Therapeutics co-founder, and CSO.

The second agreement in-licenses a humanized, tumor-specific antibody targeting an aberrantly glycosylated tumor-associated form of MUC1 (TA-MUC1) from Glycotope GmbH. Multiple solid tumor types express the mucin MUC1, including non-small cell lung cancer, breast cancer, and ovarian cancer. This antibody will be integrated into ONKs pre-clinical program ONKT103, for solid tumors.

Non-selective targeting of MUC1 could be problematic since the target is also expressed by healthy tissues, but ODwyer explains how ONKs dual-targeted approach can be used to address this. We have designed a CAR tailored to the glycosylation pattern distinct to tumor-associated MUC1 with specific recognition of the carbohydrate antigens Tn and T on MUC1, the expression of which is restricted to cancer cells. Glycotope has identified the glycosylation pattern as a way to unlock the potential of TA-MUC1 as a solid tumor target. ONK is thus set to bring the natural benefits of NK cells over T cells to bear on TA-MUC1, in a tumor-specific fashion, while also further boosting efficacy and countering resistance through the use of our TRAIL variant targeting DR5, he said.

ONKs unique platform approach combines the expression of a chimeric antigen receptor (CAR) and a high affinity, membrane-bound TRAILv. The incorporation of these two humanized scFvs has the potential to minimize the risk of immunogenicity in the allogeneic setting.

ONK is also exploring several innovative strategies to improve the homing of NK cells. This is an important consideration as ex-vivo expansion can lead to changes in chemokine receptor expression. Through this new license agreement with the NIH, ONK plans to enforce the expression of CCR7, which is downregulated on NK cell expansion. This may improve the homing of NK cells to lymph nodes and is expected to be particularly useful for ONKs off-the-shelf CD19 program targeting B cell lymphoma, ONKT101, which is partnered with Avectas.

ONK is making rapid progress since it announced its most recent financing in October. Chris Nowers, ex Kite Pharma Head of Europe, who joined at that time as Chief Executive Officer, said: The recent American Society of Hematology meeting highlighted the NK cell therapy area as offering great hope as the next generation of advanced cell therapies. We believe our best-in-class off-the-shelf, dual-targeted NK cell therapy platform has the potential to improve performance and overcome some of the shortcomings seen with earlier approaches. These new licensing activities strengthen and expand our programs and illustrate our ambition and strategy to become a leader in this exciting field.

The company recently expanded its operations into the USA, moving into JLABS @ San Diego, Johnson & Johnson Innovations flagship facility, at the heart of San Diegos precision medicine and cell therapy cluster. This represents a second facility that complements its main R&D team and operations in Galway, Ireland. The companys recruitment drive across both facilities has been rapid and the company continues to expand its capability in key areas, including NK cell biology, construct design, gene editing, and process development.

-Ends-

ONK Therapeutics http://www.onktherapeutics.com ONK Therapeutics Ltd is an innovative cell therapy company dedicated to developing the next generation of off-the-shelf, dual-targeted NK cell therapies targeting solid and hematological cancers.

The company was founded in 2015, by Prof. ODwyer MD, of NUI Galway, an expert in translational multiple myeloma research, the tumor microenvironment, and exploitation of NK cells as cellular immunotherapy. Its core proprietary platform is based on a dual-targeted NK cell expressing both a chimeric antigen receptor (CAR) targeting a known tumor antigen and a TNF-related apoptosis-inducing ligand variant (TRAILv) targeting the death receptor pathway (i.e. DR4 or DR5). This unique approach has the potential to enhance efficacy by addressing both intrinsic (e.g. CAR engagement of a tumor-specific antigen) and extrinsic (e.g. signaling through the death receptor pathway) apoptotic pathways and to reduce the susceptibility to possible target antigen escape through the engagement of tumor antigen-independent TRAILv.

Its pre-clinical pipeline comprises four programs;

In addition to the unique dual-targeted NK cell therapy platform, the company has a strong research focus on strategies to enhance homing and persistence, and overcome exhaustion, including the exploration of proprietary gene edits, such as the deletion of checkpoint inhibitory receptors in NK cells.

ONK Therapeutics is headquartered in the med-tech hub of Galway, Ireland, with a wholly-owned US subsidiary, ONK Therapeutics, Inc. based at JLabs @ San Diego. Shareholders include Acorn Bioventures, ALSHC (principally Seamus Mulligan), and Enterprise Ireland.

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About Avectas - http://www.avectas.com Avectas is a cell engineering technology business that has developed a unique delivery platform, Solupore to enable the ex vivo manufacture of cell therapy products, which have high in-vivo functionality.

Glycotope http://www.glycotope.com Glycotope is a biotechnology company utilizing a proprietary technology platform to develop highly tumor-specific monoclonal antibodies called GlycoBodies. GlycoBodies bind to targets (GlycoTargets) tumor-specific carbohydrate structure dependent, enabling the development of highly-specific immunotherapies across a broad range of cancer indications. Glycotope has to date discovered in excess of 150 GlycoTargets with GlycoBodies against eight of these targets currently under development.

Each GlycoBody can be developed in an array of modalities with different modes of action providing a unique offering in the (immuno) oncology space. Currently, six clinical and pre-clinical programs based on the GlycoBody technology are under development by Glycotope or its licensing partners.

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ONK Therapeutics Announces Three Exclusive Option License Agreements, Which Extend and Strengthen its Dual-Targeted NK Cell Therapy Pipeline -...

Cell Biology

Cell Biology – Organelles, Cycles and Division, Signaling …

Organelles, Cycles and Division, Signaling & Techniques

As a sub-discipline of biology, cell biology isconcerned with the study of the structure and function of cells. As such, itcan explain the structure of different types of cells, types of cellcomponents, the metabolic processes of a cell, cell life cycle and signalingpathways to name a few. Here, we shall look at some of the major areas of cellbiology including some of the tools used.

Cell Theory is a basic principle in biologythat was formulated by Thodor Schwann, Matthias Schleiden and Rudolph Virchow.

According to the Cell Theory:

Recently, the theory was modified to include thefollowing ideas:

A cell is a basic unit of life. This simplymeans that a cell is the smallest unit of a living thing. While some organismsare only made up of a single cell (bacteria, yeast etc) others aremulticellular organisms made up of manycells.

While there is a clear difference between unicellular and multicellularorganisms, some organisms may transition from unicellular organisms tomulticellular organisms under certain conditions.

A good example of this isslime mold that tends to transition to a multicellular organism under stressfulconditions. However, they are simply described as being partiallymulticellular. Therefore, the cell is the basic building block of any given organism.

For a multicellular organism, cells are specialized, which means that they havedifferentiated to carry out given functions.

The following are examples of specializedcells:

Sperm Cells - Sperm cells serve to fertilize the female eggto form the embryo.

Red Blood Cells - Red cells contain aprotein molecule known as hemoglobin and serve to transport oxygen to all partsof the body and expel carbon dioxide from the body.

White Blood Cells - There are differenttypes of white blood cells that serve to protect the body from disease causingorganisms.

- Basophils, Lymphocytes, Neutrophils, Monocytes, Eosinophils

Cardiomyocytes - These are cardiac muscle cells that make upthe heart muscle.

Nerve Cells (neurons) - These are cells of thenervous system that transmit information to and from different parts of the body(information is transmitted as electric and chemical signals). See also Sensory Cells.

Any given cell will have three major components.

These include:

Cell Wall

The cell wall is a complex, highly organized structure that defines the shape of a plant cell (it is also found in bacteria, fungi, algae, and archaea). In addition to defining the shape of plant cells, a cell wall has a few other functions that include maintaining the structural integrity of a cell, acting as a line of defense against a variety of external factors as well as hosting various channels, pores and receptors that regulate various functions of a cell. As such, it is a multifunctional structure in plant cells that also contributes to plant growth.

See Plant Biology.

Cell Membrane

Also known as the plasma membrane, the cellmembrane is a bi-lipid membrane layer (it is a double membranous structure)that is also composed of proteins and carbohydrates. This fluid like structureencircles the cell thereby containing the contents of a cell.

It's alsoselectively permeable, which means that it only allows certain materials(nutrients and minerals etc) to pass through to sustain the cell. The cellmembrane also functions to protect the cell and ensure stability.

Nucleus

The nucleus may be described as the largestorganelle of a cell. The nucleus is itself surrounded by a double membrane(nuclear envelope) and contains genetic information (genes) making it thecontrol center of a cell. As such, it controls such activities cell metabolismand reproduction.

Cytoplasm

The cytoplasm is the fluid matrix (jelly-like)found inside the cell (outside the nucleus). Various types oforganelles and minerals (salts) are suspended in this constantly streamingfluid. Apart from containing all the cell organelles, the cytoplasm also helpsmaintain the shape of a cell.

Cell organelles may be described as cellsubunits specialized to carry out given functions within the cell. There aredifferent types of organelles in cells that carry out given functions.

Thefollowing are some of organelles that can be found in a cell (excluding thecell membrane, cytosol and nucleus which are mentioned above):

Mitochondria - The mitochondria are rod-shaped organellesand sites of ATP synthesis. The mitochondria is also surrounded by a doublemembrane (with the inner membrane being highly folded forming the cristae).

Thisorganelle is commonly referred to as a power- generator given that it convertsoxygen and nutrients in to a chemical energy known as ATP (adenosine triphosphate)which provides the energy required for various activities of the cell. Apartfrom being a site for ATP synthesis, the mitochondrion is also involved in theself-destruction of a cell in a process known as apoptosis.

Ribosomes - Found in the cytoplasm and the surface of the rough endoplasmicreticulum, ribosomes are composed of RNA and proteins. They may be described asthe "cell factories" given that they are responsible for the synthesisof protein molecules.

Lysosomes - These are sac-like structures that are surrounded by amembrane (a single membrane). Lysosomes contain digestive enzymes, which areresponsible for breaking down proteins, lipids and nucleic acids. In addition,lysosomes are also involved in the removal of waste molecules as well asrecycling of molecular subunits.

Golgi body - These are flattened structures in a cellresponsible for temporary storage of protein in the cell.

Vacuoles - Vacuoles are also enclosed by a membrane and function to storesuch material as food, water, minerals and waste products among others.

Some of the otherorganelles include:

Cell cycle refers to a sequence in activelydividing cells where the cells pass through several stages before ultimatelydividing.

The stages of cell cycle include:

At GI, the metabolic changes take placepreparing the cell for the division process. At a given point known as therestriction point, the cell is committed to cell division and moves to the nextphase.

S - The S phase involves DNA synthesis. It isduring this phase that the replication of genetic material starts with each ofthe chromosome having two chromatic sisters.

G2 - During this phase, there are metabolicchanges that assemble the necessary cytoplasmic materials for the mitosisprocess and splitting of the mother cell.

M - The M phase is where nuclear division takes placeand followed by the division of the cell.

For most animals, cells may divide by mitosis ormeiosis. While the two processes result in the production of new cells, they aredifferent and produce different daughter cells.

Mitosis is the type of cell division that occursin all somatic cells. These are the types of cells that make up the bodytissues (apart from gametes/sex cells). Therefore, the primary role of mitosisis growth and replacing worn out cells.

Essentially, mitosis results in diploid cellsfrom one cell. Here, the chromosome is copied followed by the separation of thecopies on different sides of the cell before the cell ultimately separates intotwo. In the end, each of the new cells has a copy of the chromosome.

See more on chromosomes.

Mitosis has 5 major phases, which include:

Interphase - Here, the DNA strand is replicated/copied toproduce what is known as a bivalent chromosome (consisting of two chromatids orDNA strands that are replicas of each other). During the interphase stage, thenew strand is attached to the original one at a point known as the centromere.

Prophase - This is the second stage of mitosis. Here, the bivalentchromosomes formed during interphase condense to form tight packages.

Metaphase - This is the third stage where each of the chromosome line upat the center of the cell. The nucleus membrane has already started dissolvingwith each of the mitotic spindles attaching themselves to each of thechromatids. Here, it appears as if the chromatids are being stretched towardseither pole of the cell.

Anaphase - During anaphase, the fourth stage of mitosis, the chromatidsthat had attached to the spindles are separated (the chromatids are separatedfrom their copies) and pulled to either side of the cell. This results in twogroups of monovalent chromosomes.

Telophase - At the end of anaphase, another stage starts where nuclearmembranes start to form around the two formed groups of chromosomes. Thespindle fibers that attached to the chromatids get disassembled. Here, thechromosomes also condense.

Eventually, the cytoplasm divides/splits with a cellmembrane forming on each of the two daughter cells. This process is known ascytokinesis. Each of the new cellshas 46 monovalent chromosomes and has identical genetic information as theother.

In mitosis, it's important that the samegenetic information is copied when forming new cells. This is because the chromosomeshave all the information concerning the function of the cell.

Successfulcopying of information on to the new cells ensures that the new cell functionsproperly. In the event that there is a problem, then the new cell will be unableto perform its function as it should be. This would result in complicationsdepending on the function of the cell.

Unlike mitosis, meiosis produces haploid cells.

Diploid - Two new daughter cells from the original cell with the samenumber of chromosomes.

Haploid - With meiosis (a reductive type of cell division) the resultingcells will have less number of chromosomes.

Stages

Meiosis is also different from mitosis in thatthere are two phases of cell division. These are meiosis I and meiosis II.

Prophase 1 - Here, the homologous chromosomes pair and exchangeDNA form recombinant chromosomes. This stage ends with the spindle fibersstarting to form to attach to the chromosomes.

Metaphase 1 - The bivalent chromosomes arranges double rowhaving attached to the spindlefibers.

Anaphase 1 - The homologous chromosomes (in each bivalent)are separated and move to opposite poles of the cell.

Telophase 1 - With the separation of the chromosomes, anuclear membrane starts to form around the two groups of the chromosomes. Thisis followed by cytokinesis where the cell splits to form two new cells. This isagain followed by meiosis II. Meiosis II follows the same process as meiosis I.However, this halves the number of chromosomes.

* Meiosis is an important process that results ingenetic diversity.

What are the differences between Meiosis and Mitosis?

All cells originate from a single cell (a singlefertilized egg). In cell differentiation, cells become specialized as the bodydevelops. Apart from the single original cell (the fertilized egg), stemcells are also unspecialized. However, under certain conditions, they candifferentiate to become specialized cells that serve a specific function(s).

Although the differentiated somatic cells are different in that they performdifferent functions, they contain the same genome. However, the different typesof cells only express some of these genes, which results in the differencesmorphological and physiologicalbetweenthem.

In cells, signal transductions involve thetransmission of molecular signals. This is particularly from the exterior ofthe cell to its interior for appropriate cell response. Signals (biochemicalchanges) may either come from the environment the cell is in or from othercells that trigger changes.

Cells have receptors on the surface of the cell,which receives the signal prompting a response. For a response to take place,the signal has to be transmitted across the cell membrane.

Some of the common intracellular messengersinclude:

Cell signaling is very important given that ithelps control and maintain the normal physiological processes in the body.Different signaling processes will result in varying responses including celldifferentiation, proliferation of cells as well as metabolism among others.

Cell biology is largely concerned with the study of the structure and functions of cells (morphological and physiological). For this reason, a number of techniques have to be employed.

Some of the main cell biology techniques include:

Cells and tissues can be cultured usingcomplex media. With cells and tissues from more complex organisms, the culturemedia has to be more complex so as to provide the same environment as theenvironment from which the cell/tissue was obtained.

As for the tissue, theculturing process also allows for single cells to be obtained from the tissuein question for more studies.

The culture process requires the following:

Cell culture is an important technique giventhat it allows for only a sample (cells or tissue) to be used to learn moreabout the cells without the need to use the organism as a whole. This alsogives scientists a great opportunity to study the cells under varyingconditions.

See Also: Cell Culture

Microscopes have been used since the 1670s to observecells. Today, microscopes have become indispensable tools in cell biology. There are many more microscopy techniques today that have allowed for better viewing of cells.

In recent years, the world of microscopy hasexperienced advancements in imaging technologies enabling increased amountsof information for microscopic analysis.

Some of the most common techniques used in cellbiology include:

Staining goes hand in hand with microscopy.Although it may be regarded as an important part of microscopy, staining isitself very useful in cell biology. It allows for increased contrastwhich in turn allows for scientists to view different parts of a cell clearly.

Although staining is highly useful when it comes to viewing specimen under themicroscope, it cannot be used when a scientist wants to observe living cells.

Cell biology is an important discipline that hasallowed for viewing and studying of cells for decades now. It has become particularlyimportant to differentiate and determine different types of cells, cellprocesses as well as understanding of various diseases and illnesses associatedwith cell malfunctioning.

With advancements in various cell biology techniques,it is becoming easier to learn more about cells and cell processes foreffective intervention where necessary.

More on Cells:

Eukaryotes - Cell Structure and Differences

Prokaryotes - Cell Structure and Differences

Protists - Discovering the Kingdon Protista in Microscopy

Diatoms- Classification and Characteristics

Fungi - Mold Under the Microscope, Aspergillus type

Algae - Reproduction, Identification and Classification

Protozoa - Anatomy, Classification, Life Cycle and Microscopy

Bacteria- Morphology, Types, Habitat, looking at anaerobes, Eubacteria

Archaea - Definition, Examples, Characteristics and Classification

The rest is here:
Cell Biology - Organelles, Cycles and Division, Signaling ...

Cell Biology

Cell atlas helps better understand the biology of tropical disease parasite – News-Medical.net

The first cell atlas of an important life stage of Schistosoma mansoni, a parasitic worm that poses a risk to hundreds of millions of people each year, has been developed by researchers at the Wellcome Sanger Institute and their collaborators.

The study, published today (18 December 2020) in Nature Communications, identified 13 distinct cell types within the worm at the start of its development into a dangerous parasite, including new cell types in the nervous and muscular systems. The atlas provides an instruction manual for better understanding the biology of S. mansoni that will enable research into new vaccines and treatments.

S. mansoni has a complex life cycle that begins when larval forms of the parasite emerge from snails into rivers and lakes. These larvae then enter humans through the skin after contact with infested water. Once inside the body, the parasite begins what is known as the intra-mammalian stage of its life cycle, undergoing a series of developmental transitions as it matures to adulthood.

Adult worms live in human blood vessels and reproduce, releasing eggs that pass from the body into water to continue the life cycle. But some eggs remain trapped in the body, leading to the disease schistosomiasis.

Schistosomiasis is a debilitating long-term illness that can lead to the inability to work, organ damage and death. It affects hundreds of millions of people each year, primarily in sub-Saharan Africa, and is listed by the World Health Organization (WHO) as one of the most Neglected Tropical Diseases. Currently, only one drug is available to treat the disease, but this is inappropriate for use in very young children and there are fears that overreliance on a single treatment will allow the parasites to develop resistance to the drug.

Researchers have been looking at ways to find new drug targets, but until now there has been no high-resolution understanding of the parasite's biology.

This new study sought to map all of the cells in the first intra-mammalian stage of the parasite using single-cell technology, which identifies different cell types present in an organism or tissue.

The early-stage parasites were broken apart into individual cells that were characterized by single-cell RNA sequencing by scientists at the Wellcome Sanger Institute. The data were then analyzed to identify cell types according to the genes expressed by individual cells, and where in the body these cells were located.

The team identified 13 distinct cell types, including previously unknown cell types in the nervous system and parenchymal system. Individual fluorescent probes were made for genes specifically expressed by each cell type. Scientists at the Morgridge Institute for Research in the USA then used these probes to confirm the position of the discovered cells within whole parasites under the microscope.

Dr Carmen Diaz Soria, a first author of the study from the Wellcome Sanger Institute, said: "Though significant advances in our understanding of Schistosoma mansoni have been made in recent years, we have yet to identify targets leading to a viable vaccine. Single-cell RNA sequencing provides a whole new level of biological detail, including previously unidentified cell types, that will allow us to better understand each cell population in the parasite."

To identify new drug targets, researchers most often look for differences between a pathogen and its human host. However, S. mansoni is far closer to us in evolutionary terms than most major parasites, such as those that cause malaria. It is hoped that these findings will reveal areas of the parasite's genetic code that are sufficiently different from our own to be viable treatment targets.

Dr Jayhun Lee, a first author of the study from the Morgridge Institute for Research, Wisconsin USA, said: "We found genes in the muscular system of Schistosoma mansoni that might be specific to schistosomes. Because they are found in these parasites but not in humans, they are one possible treatment target identified by the study. The muscle allows the parasite to travel through our bodies, so if we were able to hinder that ability, we may be able to halt its life cycle before reproduction takes place."

The authors also shed light on the parenchymal tissue of S. mansoni, the 'filler' tissue that connects all the tissues of the parasite together. Previous studies had found it difficult to isolate parenchymal cells for analysis. The cell atlas found that some genes that are important for the parasite to digest food are also associated with the parenchymal tissue. Disrupting how the parasite feeds by targeting these cells could be another avenue for therapies.

Schistosomiasis is one of the most serious neglected parasitic diseases and gaining a deeper understanding of the parasite's biology will help to expose vulnerabilities that could one day be targeted by new treatments. We hope that this cell atlas for the first intra-mammalian stage of Schistosoma mansoni will provide researchers with valuable clues to help accelerate the development of new treatments and eliminate this parasite from the lives of hundreds of millions of affected people each year."

Dr Matt Berriman, Senior author, Wellcome Sanger Institute

Source:

Journal reference:

Soria, C.L.D., et al. (2020) Single-cell atlas of the first intra-mammalian developmental stage of the human parasite Schistosoma mansoni. Nature Communications. doi.org/10.1038/s41467-020-20092-5.

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Cell Biology

Glycostem and Ghent University sign license agreement on NK cell therapy technology | DNA RNA and Cells | News Channels – PipelineReview.com

DetailsCategory: DNA RNA and CellsPublished on Friday, 18 December 2020 13:05Hits: 137

- New opportunities for the development of NK-antibody combination therapies

- Significant positive effect on production time of Glycostem's lead product oNKord, and future CAR-NK and TCR-NK therapies

OSS, The Netherlands I Dec. 17, 2020 I Glycostem Therapeutics B.V., a leading clinical-stage company focused on the development of therapeutic off-the-shelf Natural Killer (NK) cells, and Ghent University (UGent) have signed a license agreement for an innovative NK cell production technology. Ultimately, this agreement will bring significant benefit to targeted treatment of patients suffering from cancer. The agreement not only opens up new opportunities for development of NK-antibody combination therapies but also has significant positive impact on the production time of Glycostem's lead product oNKord and its second (CAR-NK) and third (TCR-NK) generation therapies viveNKTM.

"This license agreement offers new opportunities for more targeted treatment of cancer patients. By using UGent's technology we are able to increase the expression of CD16 receptors resulting in an increase of the NK-cell's activity and its antibody binding properties. When a patient's immunity is weak, administering NK-cells will boost the patient's immune system and increase the antibody's therapeutic effectiveness," explains Troels Jordansen, CEO at Glycostem.

Glycostem's NK-cell based therapies are manufactured in its in-house GMP licensed facility. "Ghent University's technology has the potential to almost halve the time needed for NK cell progenitor cells to differentiate into fully functional NK-cells. By incorporating this in our processes both our manufacturing time and cost-effectiveness will be affected very positively without negative effect on the potency of the NK cells. This is an important part of paving the way for further upscaling the production of our NK-cells," says Troels Jordansen.

"We are glad to see our research translated to a clinical setting as it is based on many years of fundamental research into NK cell biology," tells Prof. Georges Leclercq, head of the UGent research team and group leader in the Cancer Research Institute Ghent (CRIG). "We hope that with this collaboration, we can positively impact the lives of many patient's affected by difficult to treat cancers."

Dr. Dominic De Groote (UGent Business Development) further explains: "This partnership is the result of continuing efforts by Ghent University and Ghent University Hospital to become a leading academic and clinical center for cell-based therapies. This technology is part of our growing portfolio of oncology and Advanced Therapy Medicinal Products (ATMP) related assets that we are actively developing from the bench to the bedside through our translational platforms."

Taking cellular immunotherapy to the next level

Glycostem is focused on developing first, second and third generation cancer treatments based on NK-cells. This licensing deal will affect Glycostem's full portfolio. After a successful phase I study Glycostem initiated a first-of-its-kind pivotal trial in acute myeloid leukemia (AML) with in-house manufactured nonmodified NK cells (oNKord). Over the coming months, AML patients will receive this form of treatment as part of a phase I-IIa trial. A pivotal phase IIa trial for Multiple Myeloma (MM) patients is expected to start second half of 2021. This makes Glycostem one of the frontrunners in this promising field of cellular immunotherapy.

About Glycostem

Netherlands-based Glycostem Therapeutics BV, a clinical stage biotech company, develops allogeneic cellular immunotherapy to treat several types of cancer. By harnessing the power of stem cell-derived Natural Killer (NK) cells, Glycostem's products are a safe alternative to CAR-T-cells. Glycostem's lead product, oNKord, is manufactured from allogeneic raw material and is available off-the shelf. Thanks to its nine patent families, longstanding technical expertise and resources, as well as 'Orphan Drug Designation', Glycostem has secured a leadership position in the global NK-cell market.

oNKord is produced in a closed system (uNiKTM) in Glycostem's state-of-the-art and GMP (Good Manufacturing Practice) licensed production facility in the Netherlands, from which it can be distributed globally. The production technology includes ex vivo generation of high numbers of NK-cells with a high degree of purity for clinical applications. oNKord successfully passed phase I clinical trial (elderly and frail AML - Acute Myeloid Leukemia - patients), providing solid safety data and strong indication of clinical activity, including response on MRD (Minimal Residual Disease). Results indicate that oNKord may be safely infused in AML patients.

Glycostem is furthermore developing a range of CAR-NK and TCR-NK products in-house and in cooperation with global partners.

Glycostem Therapeutics BV http://www.glycostem.com

Foot note: "oNKord" is a registered trademark of Glycostem in the US and in Europe. Trademark registrations of "viveNK" and "uNiK" are pending.

About Ghent University

Ghent University (UGent) is a major Belgian university located in the heart of Europe. Our organization is dedicated to research and innovation with over 5,500 researchers active in a wide area of life, physical and social sciences. Strong partnerships with the Ghent University Hospital (1000+ beds), VIB, IMEC and global leaders in academia and pharma/biotech industry thrive life science innovation at our university and is part of the thriving Belgian biotech region. Our translational platforms such as CRIG (focus on cancer) and GATE (focus on advanced therapy medicinal products) facilitate to bring science to the patient.

Prof. Georges Leclercq has a longstanding and internationally recognized expertise in differentiation and function of NK cells. The recent focus of his research group is to reveal the role of several transcription factors in the differentiation of human hematopoietic stem cells into mature NK cells, and in the maintenance and function of these mature NK cells. The ultimate aim is to attribute to improved NK-based cancer immunotherapy.

Cancer Research Institute Ghent http://www.crig.ugent.be

SOURCE: Glycostem

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Glycostem and Ghent University sign license agreement on NK cell therapy technology | DNA RNA and Cells | News Channels - PipelineReview.com

Cell Biology

ONK Therapeutics Announces Three Exclusive Option License Agreements, Which Extend and Strengthen its Dual-Targeted NK Cell Therapy Pipeline | More…

DetailsCategory: More NewsPublished on Friday, 18 December 2020 12:27Hits: 159

GALWAY, Ireland, & SAN DIEGO, CA, USA I December 17, 2020 I ONK Therapeutics Ltd, an innovative natural killer (NK) cell therapy company, today announced that it has secured three new exclusive option license agreements which strengthen its off-the-shelf, dual-targeted natural killer (NK) cell therapy platform and extend its pre-clinical pipeline to four programs across both hematological and solid tumors.

The first option agreement, with Cellerant Therapeutics, gives exclusive rights to a humanized CLEC12A scFv binder. CLEC12A is strongly expressed by blasts in the majority of AML patients. The option to license has enabled ONK to expand its pre-clinical product portfolio, launching a fourth program (ONKT104). This dual-targeted approach combines the CLEC12A CAR with a TNF-related apoptosis-inducing ligand variant (TRAILv) targeting death receptor 4 (DR4).

While expressed on leukemic stem cells, CLEC12A is absent from normal hematopoietic stem cells and we thus expect that our dual-targeted NK cell therapy approach should enable safe targeting, with a reduced risk of prolonged aplasia in AML, said Prof Michael ODwyer MD, ONK Therapeutics co-founder, and CSO.

The second agreement in-licenses a humanized, tumor-specific antibody targeting an aberrantly glycosylated tumor-associated form of MUC1 (TA-MUC1) from Glycotope GmbH. Multiple solid tumor types express the mucin MUC1, including non-small cell lung cancer, breast cancer, and ovarian cancer. This antibody will be integrated into ONKs pre-clinical program ONKT103, for solid tumors.

Non-selective targeting of MUC1 could be problematic since the target is also expressed by healthy tissues, but ODwyer explains how ONKs dual-targeted approach can be used to address this. We have designed a CAR tailored to the glycosylation pattern distinct to tumor-associated MUC1 with specific recognition of the carbohydrate antigens Tn and T on MUC1, the expression of which is restricted to cancer cells. Glycotope has identified the glycosylation pattern as a way to unlock the potential of TA-MUC1 as a solid tumor target. ONK is thus set to bring the natural benefits of NK cells over T cells to bear on TA-MUC1, in a tumor-specific fashion, while also further boosting efficacy and countering resistance through the use of our TRAIL variant targeting DR5, he said.

ONKs unique platform approach combines the expression of a chimeric antigen receptor (CAR) and a high affinity, membrane-bound TRAILv. The incorporation of these two humanized scFvs has the potential to minimize the risk of immunogenicity in the allogeneic setting.

ONK is also exploring several innovative strategies to improve the homing of NK cells. This is an important consideration as ex-vivo expansion can lead to changes in chemokine receptor expression. Through this new license agreement with the NIH, ONK plans to enforce the expression of CCR7, which is downregulated on NK cell expansion. This may improve the homing of NK cells to lymph nodes and is expected to be particularly useful for ONKs off-the-shelf CD19 program targeting B cell lymphoma, ONKT101, which is partnered with Avectas.

ONK is making rapid progress since it announced its most recent financing in October. Chris Nowers, ex Kite Pharma Head of Europe, who joined at that time as Chief Executive Officer, said: The recent American Society of Hematology meeting highlighted the NK cell therapy area as offering great hope as the next generation of advanced cell therapies. We believe our best-in-class off-the-shelf, dual-targeted NK cell therapy platform has the potential to improve performance and overcome some of the shortcomings seen with earlier approaches. These new licensing activities strengthen and expand our programs and illustrate our ambition and strategy to become a leader in this exciting field.

The company recently expanded its operations into the USA, moving into JLABS @ San Diego, Johnson & Johnson Innovations flagship facility, at the heart of San Diegos precision medicine and cell therapy cluster. This represents a second facility that complements its main R&D team and operations in Galway, Ireland. The companys recruitment drive across both facilities has been rapid and the company continues to expand its capability in key areas, including NK cell biology, construct design, gene editing, and process development.

-Ends-

ONK Therapeutics http://www.onktherapeutics.com ONK Therapeutics Ltd is an innovative cell therapy company dedicated to developing the next generation of off-the-shelf, dual-targeted NK cell therapies targeting solid and hematological cancers.

The company was founded in 2015, by Prof. ODwyer MD, of NUI Galway, an expert in translational multiple myeloma research, the tumor microenvironment, and exploitation of NK cells as cellular immunotherapy. Its core proprietary platform is based on a dual-targeted NK cell expressing both a chimeric antigen receptor (CAR) targeting a known tumor antigen and a TNF-related apoptosis-inducing ligand variant (TRAILv) targeting the death receptor pathway (i.e. DR4 or DR5). This unique approach has the potential to enhance efficacy by addressing both intrinsic (e.g. CAR engagement of a tumor-specific antigen) and extrinsic (e.g. signaling through the death receptor pathway) apoptotic pathways and to reduce the susceptibility to possible target antigen escape through the engagement of tumor antigen-independent TRAILv.

Its pre-clinical pipeline comprises four programs;

In addition to the unique dual-targeted NK cell therapy platform, the company has a strong research focus on strategies to enhance homing and persistence, and overcome exhaustion, including the exploration of proprietary gene edits, such as the deletion of checkpoint inhibitory receptors in NK cells.

ONK Therapeutics is headquartered in the med-tech hub of Galway, Ireland, with a wholly-owned US subsidiary, ONK Therapeutics, Inc. based at JLabs @ San Diego. Shareholders include Acorn Bioventures, ALSHC (principally Seamus Mulligan), and Enterprise Ireland.

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About Avectas - http://www.avectas.com Avectas is a cell engineering technology business that has developed a unique delivery platform, Solupore to enable the ex vivo manufacture of cell therapy products, which have high in-vivo functionality.

Glycotope http://www.glycotope.com Glycotope is a biotechnology company utilizing a proprietary technology platform to develop highly tumor-specific monoclonal antibodies called GlycoBodies. GlycoBodies bind to targets (GlycoTargets) tumor-specific carbohydrate structure dependent, enabling the development of highly-specific immunotherapies across a broad range of cancer indications. Glycotope has to date discovered in excess of 150 GlycoTargets with GlycoBodies against eight of these targets currently under development.

Each GlycoBody can be developed in an array of modalities with different modes of action providing a unique offering in the (immuno) oncology space. Currently, six clinical and pre-clinical programs based on the GlycoBody technology are under development by Glycotope or its licensing partners.

SOURCE: ONK Therapeutics

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Cell Biology

Op-ed: This Tampa ER doctor just got his COVID-19 vaccine and, when able, you should, too – Creative Loafing Tampa

C/O Jason Wilson, MD

By Jason Wilson, MD

Less than a year ago, I had no idea that a novel coronavirus had emerged.

Today, Ive taken care of hundreds of patients with that virus, redesigned an emergency department to safely care for patients with and without COVID-19, helped roll out 3D printed swabs to make up for a short supply of test kits, studied numerous potential viral therapeutics, found ways to virtually care for COVID-19 patients using wearable monitoring devices and telemedicine, and worked daily to show that data from our local community demonstrates that masks save lives and that we should stay out of crowded, indoor bars, restaurants and nightclubs when case numbers are high.

I can even hold my own speaking in R0 (pronounced R-naught) and exponential growth curves. Most stunningly thoughless than a year after the SARS-CoV-2 virus was genetically sequencedI have received my first dose of a COVID-19 mRNA vaccine. If given the chance, I think you should, too. Heres why.

Jason W. Wilson, MD is a clinical emergency medicine physician and critical medical anthropologist at Tampa General Hospital and the University of South Florida. Follow @tampaERdoc on Twitter.

Essential workers and vulnerable populations dont have the same option

The risk for who gets infected and who does not is partly structural and partly cultural (driven unnecessarily by heated political rhetoric and disinformation). Some people can stay at home, often struggling through web meetings, or with kids that have opted out of brick-and-mortar" for the year. Some of you have kidslike my 11-year-old currently playing Xboxon a mandatory two week quarantine after being exposed to another positive student.

Healthcare workers never could opt for safer at home, but have better access to PPE than other workers also deemed essential for service (some of whom are simultaneously deemed less essential for protection). Essential workers cannot choose to stay home. We need food and groceries, and incomes must be earned. Those essential workers are both at higher risk for contracting COVID-19, but also for transmitting the virus because of survival decisions that mean showing up to work even after exposure. Those same essential workers may also return to life in densely packed houses.A second relief packageespecially one that gives workers the tools (read: money) to stay home and not have to go out to earn a living to pay for food and rentwould help small business owners, workers and the unemployed make decisions that protect us all.

Vaccinations shouldnt be political

Equating mask requirements to an assault of freedoms, political rhetoric and disinformation are all weapons that could doom a large-scale rapid vaccine distribution campaign even before it ramps up. Couple that with more factorshistorical racism, trust of science, the vulnerability of undocumented residents, plus those weary of healthcare and Big Pharmaand you risk falling short on the herd immunity vaccines are supposed to help us reach so we get back our lives and stop this suffering.

In other words, while vaccine distribution may be political, we must ensure that vaccination remains medicine, allowing public health experts to speak loudest, tamping down on information that takes away from the clear message.

Almost everyone should get a COVID-19 vaccination

Almost everyone should get the vaccineunless you have had a significant allergic reaction to vaccines in the past. Eventually, there may be different vaccines best suited to different individuals, but right now mRNA-based vaccines are what is available and what I received. Some should get the vaccine before others (healthcare workers, long term care facility residents, EMS workers, teachers, and then older, more vulnerable people,further stratified by Centers for Disease Control and Prevention guidelines).

While there are still questions about how effective a vaccine will be for people who have weaker immune systems or take certain medications (chemotherapy, drugs like Humira, transplant meds, daily steroids), this does not mean that the vaccine is unsafe in people with weaker immune systems. It just means that the protection may not be as much given the lessened ability of immunosuppressed bodies to produce an immune response.

What about pregnant women and the COVID-19 vaccine?

We dont have a lot of data on pregnant and women who are breastfeeding since kids, pregnant,and lactating women are routinely excluded from clinical trials. However, the CDC and theAmerican College of Gynecology (ACOG)have both stated that the vaccine can be administered to pregnant and breastfeeding women and should be offered. If anything, an mRNA vaccine that leads to antibody production in a mom may convey benefit to an infant by passing antibodies through the placenta and breast milk.

What does an mRNA vaccine do?

There is a saying you learn in biology class: DNA makes RNA, and RNA makes protein. Hang with me for a second and lets do some quick Cell Bio 101.

A human cell has a nucleus inside of itlike the little rubber ball inside a baseball. That nucleus is where DNA lives. That DNAthe genetic sequence or genomeis constantly churning out a sorta mirror image middle step particle called RNA. That RNA is called mRNA (messenger RNA) because it acts as sort of a message with instructions telling the cell what to do next. The mRNA leaves the nucleus and hangs out in the celllike in the inside of the baseball, but not in the deep rubber part, just under the white leather surface.

What does mRNA do exactly? The millions of various mRNA sequences act as different instruction booklets for your cells to build all kinds of different proteinsproteins that move things around, attach to other things, make antibodies, pretty much all bodily functions.

Turns out, the surface of the coronavirus has an important protein on it called the spike protein. That spike protein is responsible for all this damage because it works by attaching the virus to human cells, allowing the virus to enter the cell, camp out and steal your cells tools to make copies of coronavirus. Spike proteins have become the major target of most of our therapies as well. The monoclonal antibody infusions people receive right now are synthetic versions of antibodies that attack spike protein.

The mRNA vaccine has the instructions to make its own spike protein to help your body mount an immune response should the coronavirus spike protein enter your system . Thats itthere are no viral particles in the vaccine, period.

What happened in the Pfizer-BioNtech vaccinestudy?

Phase three clinical trials are the big studies that directly test a new drug against a placebo or an existing treatment. On Dec. 10, the phase three study for the Pfizer vaccine was published in the New England Journal of Medicine. The major takeaway is that over 21,000 people received the vaccine and about the same number received placebo. The trial didnt examine whether a person gets COVID-19 or not, but whether a person gets sick from COVID-19 (this is why we still need to wear masks for now, even if were vaccinated). Instead, participants were followed after receiving the vaccine and were tested for coronavirus if they had COVID-19 symptoms. The mRNA technology alone was a moon-level landing breakthrough, but the results themselves matched the rigorous scientific awe! In the placebo groupthe group of people who did not get the vaccine169 people got sick with COVID-19. Among those who received the vaccine, only nine people developed COVID-19 symptoms and a positive test. In laymans terms, this means the vaccine was 95% effective in the phase three trial.

But it gets better.

Of those in the trial who had severe COVID-19requiring hospitalization, ICU level care and oxygen support, aka the really sick peoplenine were in the placebo group and only one was in the vaccine arm. Clearly, this vaccine prevents people from getting sick from COVID-19. Data released for the Moderna vaccine looks similar. And since the mRNA vaccines do such a good job of preventing symptomatic COVID-19, even those whove already had COVID-19 should be vaccinated.

C/O Jason Wilson, MD

You dont need to get tested before getting the vaccine

And, yes, getting the vaccine is definitely better than getting COVID-19 in order to obtain immunity. Having COVID-19 can not only make you very sickit also makes you very infectious.

Myth busting

How about the dangers of a new technology? Certainly, there are side effects? A few internet myths say the mRNA becomes part of your genome, or that the mRNA causes infertility (some healthcare workers who are often women of child-bearing age often fall prey to the latter).

Let me say this for the people in the back: The mRNA in this vaccine wont become part of your genome.

Remember, the mRNA is outside the cell nucleus (the inner rubber part of the baseball where the sausage making of DNA takes place). But what about all of these cells floating around with spike protein? How long will you be making this spike protein? Well, it turns out that eventually your very own cells that are making spike protein are also signing their own death warrants because that very spike protein will lead your body to come hunting for those cells as well when seeking out COVID-19 virus to destroy. In short, you wont be churning out weird spike protein cells or keeping spike protein instructions around forever (this is why we still dont know if the built in memory immunity your body gains will be enough to forgo future vaccine doses).

Let me also say this for the people in the back: The Covid Vaccine does NOT cause infertility!

I try not to engage too much in dispelling BS (because you just end up with more mounds of BS), but the nonsense that this vaccine can cause infertility must be shut down now before the rabbit hole continues to grow wider. This is an especially harmful form of disinformation because there are so many women of reproductive age on the frontlines who need this vaccine. The logic of the nonsense goes like this: A former Pfizer employee (who last worked there in 2011, but not on vaccines) notes that spike protein has some similar mRNA sequences with a broader group of proteins that support cell adherence (the process by which cells form contacts with each other). One of those similar proteins is found in humans and promotes placental growth.

Keep following me.

The logic behind the nonsense then says that since the mRNA sequences have similarities, the mRNA vaccine will cause infertility. Idaho is a state and New York is a state, so, they are basically the same, right? Wrong.

That nonsensical line of thinking falls apart pretty quickly and most easily by looking at reality. There have been millions of cases of COVID-19, but no corresponding infertility epidemic in the real world. Digging into the weeds a little more, the noted similarities are not in the area of the protein where our antibodies will attack.Myth busted!

What about side effects and the general safety of the mRNA vaccine?

As I sit here writing after my first dose, I am already developing some protectionand a little arm sorenessagainst COVID-19, and that protection will soar after I receive the second dose in 21 days (its 50% effective after dose one and 95% effective after the second dose administered 21 days later).

Seriously, am I going to grow a third eye?

What are the adverse effects, the bad things that happen? Two heads, extra arms, purple toes? The vaccine has not been around for long, and we should certainly monitor any development of downstream inflammatory mediated effects, no matter how unlikely.

OK, so tell me about side effects again.

Lets turn to the data we haveand some personal experience.

Side effects are mostly benign and seem more likely to occur after the second dose when the body is more primed to mount an inflammatory response. In fact, healthcare professionals may stagger second doses among our workforce in anticipation of some fatigue and, less commonly, low grade fevers after the injection.

On the day after I received my first dose, it felt like I got punched in the arm. In a completely unscientific poll conducted by a colleague of the other docs who received the vaccine with me, three of us had arm soreness, two docs felt completely fine and one, who had COVID-19 previously, developed some pain, skin sensitivity and a headache at the 24 hour mark48 hours later, all symptoms have resolved.

Thats it.

I had no redness, no fever, no nausea, nothing else. Like me, most people (84%, data says) will report some pain at the injection site while only about one in 20 will have any redness or swelling. One in six people may have a low-grade fever after the second dose while half feel a little tired. Symptoms like diarrhea and vomiting occurred about the same amount in the vaccine and placebo arm (about one in 50 people).

What about the more serious side effects?

A handful of medical problemsheart attacks, strokes, hospitalizationsthat occurred in the study are expected when you follow a lot of people that are older than 55 around for a few months. Its important to note that there were not any differences between the vaccine and placebo groups.

There have been a few (three as of this writing) severe allergic reactions (probably from polyethylene glycol). In at least two of those people from the U.K., each had a previous severe allergic reaction. One woman in Alaska who had an immediate reaction after receiving the vaccine had no prior allergic reactions, but remarked that very day she was still glad she got the vaccine and recommended it to others! With the whole world watching and documenting, most side effects are going to come to light and for a new vaccine moving to the arms of thousands and thousands of people, this small number of allergic reactions helps reaffirm the safety data. Per the FDA guidelines, after receiving the vaccine, all patients are monitored for 15 minutes (TGH hands out timers and lets people wait in a socially distanced space) and those with known prior allergic reactions are monitored even longer.

Does the COVID-19 vaccine cause Bellspalsy?

Bells palsy is a neurological condition that, oddly, paralyzes half of the face but usually resolves. Not surprisingly, internet myth makers have picked up on four cases of Bells palsy that occurred in the vaccine group of the Pfizer study, claiming that the COVID-19 vaccine causes Bells palsybut there is no evidence for this. There were 21,000 people in the phase three Pfizer study who got the vaccine. Bells Palsy occurs normallyon its own in about 25 out of 100,000 peoplemeaning we expected there to be five cases of Bells palsy in the vaccine group. Certainly we can ensure that this math stays true, but, for now, thats another myth debunked.

Minority enrollment, trust and transparency

Minority enrollment was an important part of the vaccine study10% of participants were African-American and 26% were Hispanic/Latino. In addition, the first person to receive the Pfizer vaccine after the FDAs emergency use authorization was a Black nurse in New York City, Sandra Lindsay. With the atrocities of Tuskegee and the horrible record of gynecological experimentation on enslaved Black bodies still in the rearview mirror, this representation of people of color is important. But will that be enough to gain trust in the vaccine?

Florida Shotsa free, statewide, centralized online immunization information systemwill help monitor who has been vaccinated. Monitoring vaccination information and linking names and personal information creates worries that undocumented people may be scared away because theyre willing to take the risks of COVID-19 and transmission to family over the fear of deportation.

There are no easy answers to the long history of exploitation against those with less power than governments and corporate conglomerates. Recognizing these issues and attempting transparency is a start. Disinformation and histories of structural violence are complicated.

Again, you should definitely get vaccinated if you have the chance

In sum, the message around COVID-19 vaccination can remain simple, persistent and consistent. The best available data demonstrates that mRNA COVID-19 vaccines from Pfizer (and Moderna) are safe and effective. Almost everyone should plan to take some version of the COVID-19 vaccine when the time comes for you to choose. If you are not in the first wave groupthose getting vaccinated before Jan. 1go get your flu shot right now and help prevent a twindemic. We dont need a flu surge on top of this ongoing COVID-19 surge.

Plan for two doses of the Pfizer-BioNtech vaccine (21 days apart) or the Moderna vaccine (28 days apart) and get the same brand of vaccine at dose one and dose two. Keep wearing your mask, keep maintaining social distance and avoid crowded indoor spaces. Help your healthcare workers help you and help this society get past a horrible pandemic.There will likely be no cost to anyone receiving the vaccine for the foreseeable future.

We will struggle with the disinformation if we do not start battling back with the set of facts that arise from reality. Disinformation drives fear and fear leads to the symbolic transformation and heated rhetoric we have witnessed among masks. Vaccines cannot become the new mask!

Support local journalism in these crazy days. Our small but mighty team is working tirelessly to bring you up to the minute news on how Coronavirus is affecting Tampa and surrounding areas. Please consider making a one time or monthly donation to help support our staff. Every little bit helps.

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Op-ed: This Tampa ER doctor just got his COVID-19 vaccine and, when able, you should, too - Creative Loafing Tampa

Cell Biology

Professor in Molecular Cell Biology job with DURHAM UNIVERSITY | 238578 – Times Higher Education (THE)

The Department of Biosciences at Durham University seeks to appoint a talented individual to the role of Professor in Molecular Cell Biology. We welcome applications from those with research and teaching interests that are consistent with research priorities in the Department and whose research is complementary to other staff in the animal cells & systems, bio-molecular interactions, or plant molecular sciences groups

The Department of Biosciences is consistently ranked in the top 5 UK Biological Sciences Departments in the Complete University Guide and was ranked 8th for Research Impact in REF2014.

We aim to appoint outstanding new academic staff to strengthen research in cross-disciplinary approaches to fundamental biological questions, potentially with impact on the bioeconomy, and to provide students with an outstanding educational and training experience. Research is focused around four key themes - animal cells & systems; biomolecular interactions; ecology, evolution & environment; and molecular plant sciences. We welcome applicants with interests in relevant areas of molecular cell biology.This post offers an exciting opportunity to make a major contribution to the development of internationally excellent research and teaching while allowing you unrivalled opportunities to progress and embed your career in an exciting and progressive institution. For more information, please visit our Department pages at https://www.dur.ac.uk/biosciences/.

We offer degree programmes in BSc Biological Sciences and a 4-year MBiol, while also contributing to Natural Sciences. Our research and teaching is supported by outstanding research infrastructure in advanced bioimaging (including super-resolution, confocal and electron microscopy), genomics, proteomics, metabolomics, high-performance computing and field research. We promote research at the interface with other disciplines.

The Department of Biosciences is particularly interested in receiving applications from women and candidates from ethnic minority backgrounds. The University is home to several networks that support researchers (e.g., women@DU, DU BAME, WHEN, and a vibrant departmental community of recent hires) https://www.dur.ac.uk/biosciences/ecrs/.

Durham University offers a generous scheme for maternity leave as well as a nursery run by the University. As an employer committed to promoting the very best talent, we also encourage applications from researchers who may have taken career breaks for family or other reasons, or who may need to consider flexible working. For more information, please visit our Department pages at http://www.dur.ac.uk/biosciences.

As one of the UK's leading universities, Durham is an incredible place to define your career while enjoying a high quality work/life balance. We are home to some of the most talented scholars and researchers from around the world who are tackling global issues and making a difference to people's lives.

The University sits in a beautiful historic city where it shares ownership of a UNESCO World Heritage Site with Durham Cathedral. A collegiate University, Durham recruits outstanding students from across the world and offers an unmatched wider student experience.

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Professor in Molecular Cell Biology job with DURHAM UNIVERSITY | 238578 - Times Higher Education (THE)

Cell Biology

Stanford Scientists Use Marlborough Company’s CODEX System in Study of Muscle Strength and Aging Published in Science – framinghamsource.com

The following is a press release from Akoya Biosciences, Inc. submitted to SOURCE through its business wire service.

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MARLBOROUGH Akoya Biosciences, Inc., The Spatial Biology Company announced that CODEX was used for spatial phenotyping to identify the source of a protein that can reverse age-related muscle atrophy.

This study represents the first demonstration of the CODEX system in imaging muscle tissues.

The paper, titled Inhibition of prostaglandin-degrading enzyme 15-PGDH rejuvenates aged muscle mass and strength was publishedonlineinScienceon December 10from the laboratory of Helen Blau, PhD, Professor and Director of the Baxter Laboratory for Stem Cell Biology at Stanford Universitys School of Medicine.

Muscle loss due to aging, called sarcopenia, is estimated to cost the US healthcare system billions of dollars each year, and results in a reduced quality of life for patients. Dr. Blau and her team are experts in investigating mechanisms of muscle structure and function related to aging and muscle disorders.

In this study of muscle fibers in mouse models and human tissue, the authors discovered an elevated level of a protein called 15-PGDH associated with old muscles. By blocking the activity of 15-PGDH in old mice, physical strength and muscle mass were restored in the animals. The opposite happened when the researchers increased the expression of 15-PGDH in young mice, causing their muscles to atrophy and weaken, as if having an aging effect. This is the first time that the protein has been associated with aging.

A CODEX assay was used to discover and understand the source of 15-PGDH, which acts as a regulator of muscle function. CODEXs multiplexing capabilities allowed researchers to look across numerous cell types and determine where the protein was localized in the tissue and which cells were expressing it. If standard methods had been used, the study would not have had the rich data of spatial phenotyping that made a difference in the results.

We adopted CODEX for this study because the platforms multiplexing capabilities simplified our search for different cell types in a tissue sample, what proteins they express and where theyre localized, said Helen Blau, PhD, Professor of Microbiology and Immunology at Stanford University. This is how we were able to identify the cells that express 15-PGDH. Were hopeful that new ways to improve health and peoples quality of life can be uncovered with the findings from this study.

Were excited that CODEX has once again supported a novel discovery and provides researchers the ability to image protein expression and cell phenotypes within their spatial context. Studying proteinsin situbrings us as close as possible to a clinical phenotype, said Brian McKelligon, CEO of Akoya. As Akoya continues to work with an ever-increasing number of researchers across the biological spectrum, we are eager to see more of these high-impact studies that help define the future of human health.

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Akoya Biosciences offers the most comprehensive, end-to-end solutions for high-parameter tissue analysis from discovery through clinical and translational research, enabling the development of more precise therapies for immuno-oncology and other drug development applications. The company has two industry-leading platforms that empower investigators and researchers to gain a deeper understanding of complex diseases such as cancer, and other immune system or neurological disorders. The CODEXsystem is the only benchtop platform that can efficiently quantify more than 40 biomarkers and is ideally suited for biomarker discovery. The Phenoptics platform is the only end-to-end multiplexed immunofluorescence solution with the robustness and high throughput necessary for translational research and clinical trials. The company has its HQ in Marlborough.

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Stanford Scientists Use Marlborough Company's CODEX System in Study of Muscle Strength and Aging Published in Science - framinghamsource.com