Category Archives: Cell Biology

Cell Biology

Aro Biotherapeutics Appoints Leading Cancer Biologist Dr. Martin McMahon and Protein Structure and Design Expert Dr. Ronald Swanson to its Scientific…

Aro Biotherapeutics announced the appointments of Martin McMahon, PhD, and Ronald V. Swanson, PhD, to its Scientific Advisory Board (SAB). Dr. McMahon will provide strategic counsel on the development of novel Centyrin-siRNA therapeutic candidates targeting KRAS and other oncogenic pathways. Dr. Swanson will provide scientific counsel on protein engineering and optimization of novel Centyrin targeting therapeutic candidates.

"We warmly welcome Dr. McMahon, a well-known leader in cancer biology and experimental cancer therapeutics, and Dr. Swanson, an accomplished protein engineer who has been involved in the development of multiple protein therapeutic candidates, to Aros SAB," said Sue Dillon, PhD, Co-Founder and Chief Executive Officer of Aro. "Dr. McMahons expertise will be invaluable to Aro as we progress our Centyrin therapeutic candidates from research into clinical development. In addition, Dr. Swansons biotherapeutics development insights and experience will be extremely helpful for lead optimization. They are both assets to Aro and our SAB."

Dr. McMahons translational cancer research program at the University of Utah focuses on the mechanisms underlying the initiation, progression and maintenance of metastatic melanoma, lung and pancreatic cancers. Prior to his appointments at the Huntsman Cancer Institute in 2015, Dr. McMahon held faculty positions dating back to 1998 at the University of California, San Francisco (UCSF) Helen Dillar Family Comprehensive Cancer Center where he served as a Distinguished Professor of Cancer Biology, Co-Leader of the Experimental Therapeutics Program and Director for Professional Education. Prior to UCSF, Dr. McMahon headed an independent research group at DNAX Research Institute in Palo Alto (now Merck Research Laboratories). He currently serves as the Cumming-Presidential Chair of Cancer Biology in the Department of Dermatology, Senior Director for Preclinical Translation and Co-Leader of the Experimental Therapeutics Program in the Huntsman Cancer Institute. Dr. McMahon graduated with a B.Sc. (Hons) in Biochemistry from Glasgow University in 1981 and a doctorate from Kings College, University of London in 1985. He completed a postdoctoral fellowship under the mentorship of J. Michael Bishop at UCSF investigating the mechanisms of action of oncoprotein kinases such as SRC, ERBB and RAF.

Dr. McMahon commented, "It is an honor to work with the Aro team to help advance transformational new therapeutics using the Centyrin technology to deliver novel cancer therapeutics directly to cancer cells. This technology has the promise to increase therapeutic anti-cancer efficacy and reduce potential toxicity to patients."

Dr. Swanson is Chief Scientific Officer at Tyra Biosciences, a company focused on targeting acquired resistance in oncology. Prior to Tyra, Dr. Swanson managed the Johnson & Johnson (J&J) Lead Discovery & Optimization group based in San Diego focused on engineering of antibodies, peptides and protein therapeutics. He was Senior Director of New Platforms and Technologies before retiring from J&J last year to return to a biotech startup environment. He began his career as Director of Genomics and Protein Expression at then biotech startup Diversa working on enzyme discovery and directed evolution. He later joined the newly founded Syrrx as Director of Molecular Biology focused on high-throughput protein structure determination and structure-based drug design. He was co-founder and CSO at ActiveSight, a pioneering structural biology contract research organization. Dr. Swanson graduated from University of California, San Diego with a BA in Biochemistry and Cell Biology in 1985 and from University of California, Berkeley in 1991 with a PhD in Molecular Biology under the guidance of Alex Glazer studying post-translational modifications of proteins. His postdoctoral fellowship was done with Mel Simon at Caltech working on protein-protein interactions in signal transduction and thermostable proteins.

Dr. Swanson commented, "It is great to be involved with the Aro team developing a novel platform for truly differentiated new therapeutics. The ability to access intracellular targets with the Centyrin technology allows for engineering highly specific and stable therapeutics that will profoundly impact disease treatment."

Story continues

Building a Pipeline of Life Changing Therapies

Centyrins are small, structurally simple, ultra-stable, highly soluble proteins. These characteristics enable the discovery of medicines with new mechanisms of action for cancer and other devastating diseases. Aros lead program is a bi-specific Centyrin-siRNA conjugate in late-stage lead optimization for KRAS mutant cancers. This first-of-its-kind combination is designed to address unmet medical needs by targeting drug payloads in high concentration to the site of disease, while lowering the toxicity to non-target organs. The company holds an exclusive worldwide license for research, development, manufacturing and commercialization of Centyrin protein therapeutics.

About Aro Biotherapeutics

Aro is a biotechnology company focused on the research and development of a new generation of protein biologics called Centyrins. Centyrins are ideal targeting moieties that enable cell specific uptake of biological payloads. The company is developing a wholly-owned pipeline of Centyrin conjugates for oncology and immunology. For more information, visit http://www.arobiotx.com.

CENTYRIN is a trademark of Johnson & Johnson.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200211005085/en/

Contacts

Media Contact Mike BeyerSam Brown Inc.mikebeyer@sambrown.com 312-961-2502

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Aro Biotherapeutics Appoints Leading Cancer Biologist Dr. Martin McMahon and Protein Structure and Design Expert Dr. Ronald Swanson to its Scientific...

Cell Biology

Diverse Biotech selected to present at upcoming BIO Meeting and announces new Gene Expression Paper Publication – WFMZ Allentown

DOYLESTOWN, Pa., Feb. 10, 2020 /PRNewswire/ -- Diverse Biotech, Inc. http://www.diversebiotech.com has announced it has been selected to present at the upcoming BIO CEO & Investor Conference in New York on February 11th. https://www.bio.org/events/bio-ceo-investor-conference/sessions/659395

In addition, Diverse Biotech has announced that a paper regarding cannabinoid-related gene expression was accepted by the Journal of Applied Cell Biology.The paper should be published in the next 3-4 weeks.

"We are truly excited to continue to discuss our ground-breaking technology.In addition, the gene expression paper is tremendous because it highlights that a variety of cell lines including glioblastoma, pancreatic cancer, melanoma, actinic keratosis, squamous cell carcinoma, and normal skin all express genes that suggest they will be responsive to exogenous cannabinoid treatment," saidStella Vnook, Diverse Biotech's Chief Executive Officer.

About Diverse Biotech

Diverse Biotech is a US-based biopharmaceutical company, focused on medical discoveries and the development of new molecules for the treatment of Cancer and other debilitating diseases.Our focus is on discovering and developing novel therapeutics utilizing cannabidiol (CBD) as a core component and combining it through highly advanced chemistry with other molecules to develop new chemical entities that are theoretically more efficacious and less toxic. Our initial focus is on hard-to-treat oncologic disorders including basal cell carcinoma and other Dermatology related cancers, Pancreatic cancer and Glioblastoma, where targeted therapies have proven largely unsuccessful thus far and there is significant unmet need.

Further information about Diverse Biotech can be found at http://www.diversebiotech.com.

Contacts:Brian LongstreetChief Business OfficerDiverse Biotech, Inc+1-908-917-5699blongstreet@diversebiotech.com

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Diverse Biotech selected to present at upcoming BIO Meeting and announces new Gene Expression Paper Publication - WFMZ Allentown

Cell Biology

Synthetic biology is shaking up these 5 industries-Some of them might surprise you – SynBioBeta

Ask any researcher for a definition of synthetic biology, and youll get a different answer. Synthetic biology is an incredibly diverse field with applications that span the biotechnology gamut. But what makes the field difficult to define also makes synthetic biology a wellspring of opportunities for jobseekers. In this post, we highlight a few of the growing fields where burgeoning synthetic biologists can expect to find job opportunities.

The oldest application of biotechnology is arguably biomanufacturing of insulin. Scientists discovered how to co-opt yeast and bacteria into producing human medicines decades ago. But while producing insulin only requires a single gene, there are many important medicines such as taxol (an anti-cancer drug) that require entire pathways. Thats where synthetic biology comes in.

There are a multitude of companies using synthetic biology to engineer pathways that enable microorganisms to produce medically relevant drugs. Famously, Amyris engineered yeast to produce the antimalarial drug Artemenisin. Synthetic biology can also improve in-vitro drug manufacturing. For instance, Codexis uses synthetic biology to develop more efficient enzymes for synthesis of small molecule drugs.

Beyond biomanufacturing of drugs, there are many other ways to apply synthetic biology to biopharma research. For instance, there are several companies engineering microbes not only to produce medicines, but to deliver them in vivo. These so-called engineered probiotics could potentially be tuned to produce drugs in response to a particular stimulus or only in certain parts of the body.

As science reveals more about the microorganisms living in and on us, companies are developing microbiome-based therapeutics to target a litany of diseases. Skin microbiome company Azitra shares their approach to effectively developing, testing, and bringing microbiome-based therapeutics to the clinic. Image source: Azitra

Companies are also engineering human cells for therapeutic purposes. This is the basis for CAR-T cell therapy, a promising new approach to cancer treatment. Beyond single cells, some companies are focused on developing synthetic tissues and whole synthetic organoids for research or therapeutic purposes.

Companies to watch:

A major goal of the synthetic biology industry is to develop alternative, biology-based methods for industries that typically use petroleum-based products as inputs and produce carbon emissions as outputs.

There are many companies working to produce biofuels or bioplastics. For instance, Synthetic Genomics is engineering algae as biofactories for renewable fuel, and Global Bioenergies is developing processes to ferment plant waste into petrochemical precursors.

Others are working to fix carbon more directly by attempting to optimize natural carbon-fixers (plants and cyanobacteria). Long-term carbon storage is also a challenge, and its one some synthetic biologists think bacteria can solve by converting carbon dioxide into a liquid state.

Carbon emissions dont only come from burning fuel, however. There are also biological and environmental sources of greenhouse gas. LanzaTech sees these sources as a useful starting point for making high-value chemicals. Its carbon recycling technology platform captures and converts so-called biogas from agricultural and municipal waste, then converts it to biofuels and other products.

Together, these efforts comprise what could make up a circular economy in which biology is both the source and the byproduct of many of the products that we depend on instead of petrochemicals.

Companies to watch:

Carbo Culture is pioneering a product to tackle both agricultural air pollution and soil degradation. Biochar plays an active role in a balanced carbon cycle.

We dont often think about the science behind our clothing, but if you look at the tags of anything youre wearing right now, youll probably be reminded that fashion is fed by a complex mashup of materials. Clothes are a mixture of plant-based materials (like cotton), petroleum-based materials (like nylon and spandex), and animal-based materials (like leather and silk). The fibers that make up our garments are also almost always bleached or dyed and chemically treated. With all of this complexity, fashion can have a bit of a nasty environmental footprint.

There are several companies using synthetic biology to come up with greener alternatives for fashion must-haves. For instance, Tinctorium, PILI, and Colorifix are finding a way to dye blue jeans without producing hazardous waste. In addition, Mango Materials is using bacteria to turn methane into bioplastics for clothing and other goods that will degrade naturally if they end up in our oceans as so much waste does.

Sourcing colors from a range of natural pigments, Colorifix engineers microorganisms to convert agricultural by-products into dyes. When the microorganisms burst they fix the colour to the fabric, thus reducing the need for massive amounts of water, according to BBC Earth. Photo by Marianna Limas

Even fashion icons are taking notice. High fashion designer Stella McCartney is bringing synthetic biology to the runway by partnering with Bolt Threads, a synthetic biology company endeavoring to make synthetic silk and faux leather from mushrooms. Bolt is not alone; synthetic silk companies are popping up all over the world, including AMSilk in Germany and Spiber in Japan, and theres a company in New York called Ecovative Design thats using mushrooms to create all sorts of materials for clothing, footwear, and beyond.

Companies to watch:

Your clothes may not be the only thing youre wearing that will soon be shaped by synthetic biology. There are also synthetic biology companies targeting makeup, skin creams, cologne, and perfume.

Traditional ingredients for cosmetics are often animal-based, raising purity and animal rights concerns. For example, collagen is a popular ingredient in high-end anti-wrinkle creams, because its responsible for skin elasticity. But collagen is sourced from animals, meaning its not vegan-friendly, and it can elicit purity and allergy issues. Geltor is using synthetic biology to produce animal-free collagen substitutes. Biossance, an Amyris spinoff, has also used synthetic biology to create an animal-free cosmetic additive, squalane, which was traditionally harvested from shark livers.

HumaColl21 is just one example of how a biodesigned future leads to better products for improving peoples lives. Image: Geltor

In addition to taking an environmental toll, ingredients for cosmetics and, especially fragrances, can be incredibly expensive. The essence of grapefruit is captured by a flavor compound called nootkatone. At about $200 per gram, true, pure nootkatone is limited to higher end colognes. A synthetic biology company called Evolva wants to change that by producing nootkatone and other fragrance compounds via fermentation. Conagen is also using microbial fermentation to produce high-value flavors and fragrances such as vanillin, while Motif Foodworks (a spinout of synthetic biology unicorn Ginkgo Bioworks) is also brewing up new sources for fragrances such as the essence of a rose.

Companies to watch:

This category deserves several posts all its own. Synthetic biology companies are reimagining the food space in several ways from revolutionizing agriculture to tackling food waste to coming up with more environmentally-friendly sources of food additives.

Starting with the plants in the ground, companies like Pivot Bio and Joyn Bio are engineering soil bacteria to end our dependence on synthetic fertilizers.

Other synthetic biology companies are focused on what happens to food after its harvested. For example, Conagen is engineering strains of microorganisms and novel enzymes to synthesize all sorts of food-additives from food colorings, to sweeteners, to meat tenderizers, to preservatives.

But companies arent just focused on solid ground. AquaBounty, for example, is combining advances in aquaculture with modern genetics to create the worlds most sustainable salmon, while Air Protein is using bacterial fermentation to make protein from the elements comprising the air we breathe.

Several companies, such as Memphis Meats and Meatable, are allowing us to have our animals and eat them too, using synthetic biology to create real meat without harming animals or the planet.

Companies to watch:

The limited run of Perfect Day ice cream is already sold out, but it showed big food producers how microflora can be used to produce animal-free ingredients for milk, dairy, cheese, and ice cream. Image: Perfect Day Foods.

The five synthetic biology focus areas highlighted here are far from an exhaustive list. And for every company working on a specific application, there are others like Evonetix, Twist Bioscience, Inscripta, Ginkgo Bioworks, and Benchling that are building the DNA synthesis, editing, organism engineering, and data tools that the entire synthetic biology industry depends on.

While synthetic biologists offer varying definitions of the field, most will agree that an overarching goal of the industry is to shift our reliance away from chemistry and fossil fuels and towards biology. Its a lofty goal, but with so many diverse companies working to support it, synthetic biology will have a major role in shaping the future of technology across industries.

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Synthetic biology is shaking up these 5 industries-Some of them might surprise you - SynBioBeta

Cell Biology

Bacteria, bone and more: Here’s the science launching to the space station Sunday – Space.com

NASA is launching a bevy of crew supplies and scientific cargo to the International Space Station Sunday (Feb. 9) from NASA's Wallops Flight Facility in Virginia.

Perched atop an Antares rocket will be a Northrop Grumman Cygnus cargo spacecraft, and tucked inside will be nearly 8,000 lbs. (3,600 kilograms) of supplies and hardware. The capsule will bring supplies for the crew currently living on the space station.

Also onboard the spacecraft will be a variety of experiments and pieces of research equipment. These will support investigations on topics including tissue and cell cultures and biofuels.

In photos: Antares rocket launches Cygnus NG-12 cargo craft to space station

A new miniature biology lab is headed to the space station on the Cygnus capsule. Dubbed the Mobile SpaceLab, the system is a technology-demonstration project that scientists hope could demonstrate a new way to conduct experiments in orbit. That's because Mobile SpaceLab is a tissue- and cell-culturing facility designed to function autonomously, running an experiment for up to one month without using precious astronaut time.

Developed by HNu Photonics, a Hawaii-based engineering company, the Mobile SpaceLab will offer researchers a quick-turnaround, automated platform to conduct cutting-edge biology experiments in microgravity. The facility is remote-operated by crews on the ground, and the automation enables researchers to observe cellular functions with a technique called microscopy.

The ability to observe cell cultures in microgravity will provide the researchers with real-time data about how tissues behave in space. Microgravity better mimics how a cell behaves in the human body than any artificial environment on the ground.

During this initial mission, the team is sending up neuroblastoma cells a type of nerve-cell cancer. Specifically, the experiment will study how cells mature, which biologists call cellular differentiation, and how microgravity affects that process.

"Gravity is a fundamental force that we're all subjected to here on Earth," Devin Ridgley, chief scientist at Scorpio-V, said during a NASA news conference held on Jan. 29. "It can have a drastic effect on how a cell differentiates, which affects cellular organization and communication and can lead to cognitive decline." He added that the experiment could help scientists better understand the effects of space travel on the brain.

A team from the University of Alaska will be sending a batch of genetically engineered E. coli bacteria to the space station. Here on Earth, the organisms can produce a compound called isobutene, which is a precursor to plastic and rubber and can be used on its own as a biofuel.

These bacteria can produce isobutene by feeding on wastewater, manure and the mess left over from corn harvests. So, using bacteria to make the material would sharply contrast with current methods of making isobutene, which require high-energy chemical reactions and petroleum-heavy ingredients.

But the bacteria make only very small quantities of the compound, so researchers want to identify how the organisms produce isobutene, in hopes of genetically increasing production rates. To better understand how this process works, the researchers will look at a group of genetically enhanced E. coli and study how effectively the bacteria produce isobutene compared to their terrestrial counterparts.

The bacterias metabolic activity changes in microgravity, so the researchers are trying to test whether the bacteria make more or less isobutene in space. If the scientists understand how the bacteria produce isobutene, they can genetically engineer bacteria that are more efficient, reducing the need for energy-intensive, chemical processes. This will ultimately cut down on environmental pollution, the researchers have said.

Millions of Americans lose bone mass each year due to an imbalance of bone remodeling, when the body doesnt make new bone as quickly as it absorbs older bone. The disease, called osteopenia, is the beginning of osteoporosis. Our bones have a process by which they naturally form and dissolve bone matter equally, but sometimes this process gets out of whack.

Imbalances can occur when the body is stressed, like what happens in microgravity. So, scientists want to use the space station to develop treatments to mitigate these effects, both on Earth and in space.

"Astronauts lose 1 to 2.5% of their bone mass per month," Louis Kidder, a bone biologist at the University of Minnesota and co-investigator on the project, said during the news conference. "That would take a year with osteoporosis."

He added that the microgravity environment of the space station allows for a better understanding of how bone cells respond to varying amounts of gravitational force. The group will send up osteoblasts (bone cells) to study how they react to microgravity, comparing that result to a ground-based group's behavior.

The ground-based cells will be in a magnetic levitation device that will simulate the conditions of space. If it proves to be an effective simulator, it could help researchers here on Earth better understand bone loss and enable them to develop more therapies to mitigate loss without the need for a rocket.

"The loss of bone in microgravity is accelerated compared to Earth," Bruce Hammer, a radiologist at the University of Minnesota and co-investigator on the project, said during the news conference. "With this [experiment], we can look at the mechanisms and possible therapies."

That's only a sampling of the research investigations launching aboard Cygnus. A new plant-growth experiment will look at how cowpeas, also known as black-eyed peas, and common beans grow in microgravity, as part of NASA's continuing efforts to grow food in space.

Another new study will test how radiation and microgravity affect the relationship of a virus and the bacterium it infects. The researchers hope that this study will lead to new antibacterial treatments.

Cygnus will also carry a new fire experiment, called Saffire IV, which will study how flames grow and react in a variety of pressures and oxygen concentrations. Previous iterations of this experiment have looked at how flames spread across specific materials that would likely be found on a spacecraft. This experiment will take that further by testing flammability at lower pressures and higher oxygen concentrations, to most closely mimic space conditions. The experiment will also test methods for detecting fires and for cleaning up their aftermath.

This is the second Cygnus flight under Northrop Grumman's Commercial Resupply Services 2 contract and is the first cargo delivery to the space station this year. You can watch the launch here at Space.com Sunday (Feb. 9), with blastoff targeted for 5:39 p.m. EST (2239 GMT).

Follow Amy Thompson on Twitter @astrogingersnap. Follow us on Twitter @Spacedotcom or Facebook.

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Bacteria, bone and more: Here's the science launching to the space station Sunday - Space.com

Cell Biology

LSU biologists think they’ve found breakthrough in fight against aging – Greater Baton Rouge Business Report

Two LSU biology professors have discovered a new class of cellular connections that could lead to breakthrough medical therapies and treatments to slow down, and possibly reverse, aging and disease.

Alyssa Johnson and Adam Bohnert, both assistant professors in the LSU Department of Biological Sciences and experts in cell and molecular biology, recently received a $1 million grant from the W. M. Keck Foundation for their work, according to a new LSU announcement.

The pair are researching what they call tubular lysosomes, differing from the traditional idea of a lysosome as a spherical vesiclethink SpaghettiO shape. Lysosomes are cellular garbage dumps for obsolete and unwanted materials, like bacteria and viruses.

Johnson and Bohnert found that tubular lysosomes can form complex networks between the bodys cells that greatly affect stressors like aging and disease. Not every type of tissue in the body of an organism contains these structures, but sometimes the lysosome networks are grown because of outside stressors to the organism. A part of their research tests why these networks form, and whether the tubular lysosomes can be passed on genetically from parent to child, then onto grandchildren and so on.

This is a major black box in biology where we dont have a lot of knowledge yet, Bohnert says. Tubular lysosomes could hint at ways to slow down the aging process, or even reverse it. This sounds like science fiction, but it could be possible.

Johnson was the first to find these tubular lysosomes in a fruit fly, which she routinely studies.

Theyve identified a couple of genes that could control them. The question now is whether they can introduce these genes to animals and tissues that dont normally have them.

Were really the only ones studying tubular lysosomes in the world, which puts us in a unique position to break open this field, Johnson says. Their ongoing research will now likely lead to revisions in textbooks, as it redefines our perception of life at its most basic unitthe cell. Read the full story here.

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LSU biologists think they've found breakthrough in fight against aging - Greater Baton Rouge Business Report

Cell Biology

Structure of protein filament which tethers and moves bacterial DNA revealed – BSA bureau

Singapore's A*STAR researchers have figured out the detailed structure of a type of filamentous protein ParM in C. botulinum, seeking to understand its structure and function

Better known for producing botoxa compound associated with wrinkle removal in cosmetic clinicsthe bacteriaClostridium botulinumis also studied by scientists seeking to understand fundamental biological processes such as bacterial cell division. As a bacteria cell divides, it needs to properly segregate DNA into the resultant daughter cells, a process carried out by strands of proteins.

Earlier research has shown that these protein filaments are encoded by the bacterias DNA (also called a plasmid) and that the proteins differ among bacteria species. In this study, researchers led by Robert Robinson, a Research Director at A*STARsInstitute of Molecular and Cell Biology (IMCB), zoomed in on the filamentous protein ParM inC. botulinum, seeking to understand its structure and function.

Collaborating with scientists in Japan, Robinsons group used a technique called cryogenic electron microscopy (cryoEM) to obtain high resolution (4.2 Angstrom) structural data on ParM, which revealed that it generally persists as a 35 m-long filament, with a diameter of 26 nm.

Importantly, the researchers observed that ParM is a complex of 15 loosely associated, left-handed helical, single strands. A cross-section of the 15 strands reveals a central strand surrounded by an intermediate layer of six interacting twisted helical strands running antiparallel to the central strand. The remaining eight strands form an outermost layer, running antiparallel to the six intermediate strands.

Robinson remarked that the result was surprising becauseEscherichia coli, another common model bacteria, makes use of only a pair of two-stranded ParM filaments to segregate its DNA. Hence, the 15-strand configuration of ParM inC. botulinumis likely to allow for a greater generation of force and motion.

Our findings tell us that many filament designs are used in moving plasmids. This is likely selected for during evolution since two types of plasmid existing in the same cell will require two different segregation systems to faithfully maintain both plasmids, explained Robinson.

He added that mutations affecting the structure of ParM could also influence plasmid propagation. Learning about the mechanisms controlling plasmid segregation could, in turn, shed light on how bacteria acquire certain traits, such as antibiotic resistance and toxin production.

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Structure of protein filament which tethers and moves bacterial DNA revealed - BSA bureau

Cell Biology

Virus expert and cancer biologist Harry Rubin dies at 93 – UC Berkeley

Harry Rubin in 1989. (UC Berkeley photo by Jane Scherr)

Harry Rubin, a leader in the search to understand how viruses cause cancer research that ultimately led to the discovery of cancer-causing genes called oncogenes died on Sunday, Feb. 2, at the age of 93. Rubin was a professor emeritus of molecular and cell biology at the University of California, Berkeley.

A veterinarian by training, Rubin began investigating in the 1950s how normal cells turn into cancer cells a process called transformation. This was at a time before genes could be cloned and sequenced, and much of his research relied on manipulating cultured cells in a petri dish.

Many labs were beginning to work with tumor viruses as the only tractable way to understand cancerous transformation, and Rubin chose to focus on a virus known since 1911 to cause cancer in chickens: the Rous sarcoma virus (RSV). RSV is an RNA virus, which means that it carries its genetic instructions in the form of RNA, not DNA. The virus tricks cells into reverse transcribing its RNA into DNA and integrating it into its own genome.

At that time, there was really no way of studying the molecular or genetic basis of cancer by studying cancer cells, because the genome of the cell is so enormous, said G. Steven Martin, one of Rubins former postdoctoral fellows and a UC Berkeley professor emeritus of molecular and cell biology. Before the advent of cloning and genetic sequencing, we couldnt look into the cancer cell and find the genes involved in cancer. Since tumor viruses have such small genomes and carry only a few genes, it was clear that studying tumor viruses would provide an entry point into the basic mechanisms of cancer.

Between 1953 and 1958, Rubin worked as a postdoctoral fellow and, later, as a research fellow in the lab of virologist Renato Dulbecco at the California Institute of Technology in Pasadena. In 1955, Rubin showed that every cell in an RSV-induced tumor was capable of releasing the virus, implying that RSV was permanently associated with the host cell and suggesting that it plays a direct and continuing role in perpetuating the cell in its malignant state.

Then, working with Caltech graduate student Howard Temin, Rubin developed a way to measure the amount of infectious virus using cultured fibroblast cells from chicken embryos. This opened the way for quantitative studies of the mechanism by which RSV transforms normal cells into cancerous cells.

Dulbecco and Temin later shared the 1975 Nobel Prize in Physiology or Medicine for their work on tumor-causing viruses.

When Rubin moved to UC Berkeley in 1958 to join the Department of Virology, he continued work on RSV and developed other assays, including one to detect avian leukosis virus in vaccines, such as the measles vaccine, that are produced in chicken cell cultures.

Harry Rubin and his wife Dorothy.

He also showed that one strain of RSV was a replication-defective virus that could transform normal cells into cancer cells, but required a leukosis virus a helper virus to replicate and spread. In other words, the RSV could transform, but not replicate, itself, while the helper virus could replicate, but not transform.

This was one of the very first observations to suggest that the virus might carry information about cell transformation and tumorigenesis that was separate from the information needed for the replication cycle of the virus, Martin said.

Rubins work on RSV earned him a prized Lasker Award in 1964.

The work of Drs. Rubin and Dulbecco proves that cells can carry, for many generations, a foreign nucleic acid, whether RNA or DNA, that is responsible for the malignant properties of these cells, the Lasker Foundation wrote in giving them the award in clinical research.

Rubin also received the 1961 Eli Lilly Award in Bacteriology and Immunology and the 1963 Merck Research Award for his work on RSV and was elected to the National Academy of Sciences in 1978.

In 1970, a viral gene responsible for cancerous transformation, now known as viral src, or v-src, was identified through genetic and biochemical studies on RSV carried out by Martin, who was then in the Rubin lab, Peter Vogt at the University of Washington in Seattle and Peter Duesberg at UC Berkeley. This allowed Harold Varmus and Michael Bishop of UC San Francisco to identify an analogous gene in the cellular genome a gene evidently stolen by the Rous sarcoma virus. Called cellular src, or c-src, it was the first known proto-oncogene, that is, a normal gene that, when mutated, can trigger cancer. Many more proto-oncogenes have been discovered since then. The discovery won Bishop and Varmus the 1979 Nobel Prize in Physiology or Medicine.

The significance of the work on the Rous sarcoma virus is that it led to the work on cellular genes that can cause cancer, Martin said. The idea that, by studying the virus, one could get an insight into the cellular and genetic mechanism of carcinogenesis was, in fact, vindicated.

Although Rubins research set the stage for the discovery of oncogenes, by the early 1970s he had switched his focus from viruses to the biology of transformed cells, looking at the mechanisms of growth control and, in particular, the role of inorganic ions in cellular regulation. In later years, he studied the origin of spontaneous transformation of animal cells in culture, using this system as a model for tumor progression.

Harry Rubin was born in New York City on June 23, 1926, the son of Russian Jewish immigrants. His father ran a grocery store in Manhattan. As a teenager, he worked on farms in upstate New York and at 16 enrolled in the veterinary school at Cornell University. Upon graduation in 1947 with a D.V.M. degree, he went to Mexico to help with an outbreak of hoof-and-mouth disease, then joined the U.S. Public Health Service in Montgomery, Alabama, to work on viral diseases, including rabies and Eastern equine encephalitis. In a 1991 profile in California Monthly magazine, he referred to it as time spent chasing cows and horses in Mexico and Louisiana.

Seeking new challenges, he enrolled at New York University and, a year later, in 1952, convinced Nobel Prize winner Wendell Stanley to let him work in his Virus Laboratory at UC Berkeley. Rubin transferred to Caltech in 1953, returning to join the UC Berkeley faculty in 1958, where he eventually occupied Stanleys old office. He retired as an emeritus professor in 2001.

Rubin is survived by his wife, Dorothy, of Berkeley; three children, Andrew, Janet and Clinton Rubin; six grandchildren; and six great-grandchildren. He and his wife were longtime members of Congregation Beth Israel in Berkeley.

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Virus expert and cancer biologist Harry Rubin dies at 93 - UC Berkeley

Cell Biology

Is There Any Science Behind Beauty Sleep? – Labmate Online

A new study from the University of Manchester suggests the popularised term "beauty sleep" could be more than just a saying. After analysing body clocks of mice, a team of biologists maintain a good night's sleep plays an important role in preparing the body for the day ahead and replenishing cell structures.

The findings were published in the journal Nature Cell Biology and explain how body clock mechanisms support the extracellular matrix (ECM), a three-dimensional network of macromolecules that build connective tissue cells such as skin, bone, cartilage and tendons. Professor Karl Kadler, lead author of the study, argues that understanding the importance of the body clock and the extracellular matrix could shed new light on the ageing process.

Kadler explains that more than half the body is made up of matrix. Of this matrix, 50% is collagen, a key extracellular matrix structural protein and major component of connective tissues. Roles of collagen include providing the skin with structure and elasticity and strengthening bones. By the time the body reaches the age of 17 collagen has fully formed, suggesting the body starts to slowly deteriorate moving forward.

"Collagen provides the body with structure and is our most abundant protein, ensuring the integrity, elasticity and strength of the body's connective tissue," says Kadler.

Collagen is made up of rope-like structures called fibrils, which are woven together by cells to create tissues. During the research, the biologists discovered two types of fibrils. The first were relatively thick, measuring around 200 nanometres in diameter. They form by the age of 17 and stay with the body throughout its lifespan. The second type of fibril was thinner, measuring just 50 nanometres in diameter. As the body is put through its daily paces these thinner fibrils snap and become damaged. They are automatically repaired and replenished at night, with the team asserting that sleep plays a critical role in supporting this process.

"It's intuitive to think our matrix should be worn down by wear and tear, but it isn't and now we know why: our body clock makes an element which is sacrificial and can be replenished, protecting the permanent parts of the matrix."

Kadler says detailed knowledge of how the body clock influences the extracellular matrix could help scientist understand human biology at its most fundamental level. "It might, for example, give us some deeper insight into how wounds heal, or how we age," he predicts.

From exploring the role of the body clock to analysing interactions between different species, science is continually offering new insight into how the world works. To find out more about the cutting-edge composition-gradient multi-angle light scattering (CG-MALS) technique, don't miss 'Fusion Protein Complexes Analysed by CG-MALS - Non-equivalent, Multivalent Interactions.'

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Is There Any Science Behind Beauty Sleep? - Labmate Online

Cell Biology

When rocket blasts off for space station, EVMS will be along for the ride – Daily Press

Just days before a planned rocket launch, a crate the size of a dishwasher destined for the International Space Station had been routed to the wrong Norfolk address.

The mysterious wooden box held equipment for scientists at Eastern Virginia Medical School who needed to prepare it to be shot into orbit from Wallops Island on Sunday.

Instead, it sat at a senior high-rise, intriguing elderly residents with its many Hawaii labels.

The delivery mishap gave Northrop Grumman project manager JoElla Delheimer a dose of last-minute anxiety. The stress lifted when she learned that the box was only a couple of blocks away from the EVMS campus.

One thing about flying a rocket to space is that you cant be five minutes late, she said.

Through a multimillion-dollar contract, scientists are using the Norfolk medical schools laboratories and supplies to prepare experiments for astronauts. And while certain studies are done in orbit, scientists down below will conduct control experiments at EVMS.

The partnership with NASA contractor Northrop Grumman began with a mission last fall and will continue for at least three years, aiding five more space launches out of Wallops Island.

Weather permitting, Northrop Grumman plans to send up its unmanned Antares rocket and Cygnus spacecraft, carrying more than 8,000 pounds of cargo, at 5:39 p.m. Sunday from the Virginia flight facility.

So long as the Cygnus is on schedule, it will dock at the station Tuesday.

Bill Wasilenko, the vice dean of research at EVMS, said one reason the school got involved was that it would bring in researchers from around the world. On a later mission, for example, the school will host some Japanese scientists through the contract.

A lot of biomedical benefit is likely to come out of doing the research that we do up there, in terms of drug development. There are ways in which crystals develop in space that are different that could lead to new pharmaceuticals, new therapeutics, he said. The hope is our medical students will mingle around the scientists, learn about what were doing from mission to mission, come to our seminars. Maybe some of them will get interested in space medicine.

Two research teams were at the Norfolk campus this week preparing experiments and hardware for liftoff.

One group from Hawaii plans to run a tissue-culturing study in a device it developed called the Mobile SpaceLab. The equipment has a sort of set-it-and-forget-it capability: Once its at the space station, it will perform biology tests without crew. The device will take pictures of the cell activity every six minutes for four weeks.

Devin Ridgley, chief biologist for the Scorpio-V division of HNu Photonics, said the automation frees up the crew to work on other things and eliminates some of the potential for mistakes.

Weve been trained with this equipment and cell biology for many years now, but the crew may not be as well-trained, he said. Some are fighter pilots deservedly crew, but maybe not the best at doing cell biology experiments.

On Thursday at EVMS, Ridgley started growing a type of cancer cell, neuroblastoma, for the experiment. The study will look at the effects of microgravity the weak gravitational conditions of the space station at the subcellular level.

The second team, from BioServe Space Technologies based at the University of Colorado, was busy in a different lab preparing kits for another microgravity-related study. Mark Rupert, associate director of BioServe, said the hardware sort of like petri dishes that work without gravity will facilitate research on bone loss using osteoblast cells.

On Earth there is a way to levitate organisms with strong magnets, which may provide a way to study the bone loss that happens in space, he said. But its unclear if that simulation is a good substitute. The experiment, run by a researcher at the University of Minnesota, will compare the methods. If the magnet technique is suitable, it could be a cheaper way to study the problem in the future than running more tests at the space station.

Because astronauts experience bone loss in orbit, researchers want to learn more about it, not only to help future space travelers but to better understand a wide range of disorders, such as osteoporosis.

To get ready for its supporting role for NASA, EVMS sent staff down to the Kennedy Space Center in Florida to tour the facility and observe operations. There they saw things like researchers who were growing lettuce talk to an astronaut, who was also growing the leafy vegetable at the space station.

The laboratories that are needed for the pre-launch preparation of experiments primarily occur at the Kennedy Space Center, but theyre overwhelmed. They have a backlog of experiments, Wasilenko said.

That makes EVMS, a two-hour drive from the Wallops Island launchpad, well-positioned for providing similar services, especially for experiments that involve live tissue or rodents that must be packed at the last minute. Though no critters will board the Cygnus this time, about 40 mice, born and raised on campus, flew in the previous mission that took off in November.

Northrop Grumman said that no other place it considered was large enough or had the capabilities of EVMS.

One of the primary things that brought us here, of course, was the animal care facility, Delheimer said. Their reputation is tremendous.

Separate from the Northrop Grumman contract, EVMS has two NASA-funded studies. Richard Britten, an associate professor of radiation oncology and biophysics, is examining the effects of galactic cosmic radiation on brain function. And Larry Sanford, professor of pathology and anatomy, is studying in-flight stress and sleep disturbances on brain function.

EVMS administrators hope the schools new role will open opportunities for more of its own biomedical research. Wasilenko thinks its an interesting coincidence that a lot of the research coming out of EVMS right now happens to be on similar subjects as those being studied in the space station.

Diabetes, obesity, circadian rhythm work and now the bone thing, he said. "Theres a lot of overlap, and thats the appeal of researchers coming here and mingling with our researchers. If they hit it off, they could work together on some future projects.

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When rocket blasts off for space station, EVMS will be along for the ride - Daily Press

Cell Biology

Pedal to the Metal: Speeding Up Treatments for ALS – UANews

A therapeutic intervention for amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig's disease, could be on the horizon thanks to unexpected findings by University of Arizona researchers.

ALS is the progressive degeneration of motor neurons that causes people to lose the ability to move and eventually speak, eat and breathe.

Within the neuronal cells of patients with ALS and other neurodegenerative diseases, two proteins TDP-43 and FUS are often found in bundles of molecular junk called aggregates, which can accumulate to deadly levels.

Its not clear yet if TDP-43 aggregates themselves are truly toxic or a sign that things have gotten really bad in a cell, and this is its last Hail Mary trying to keep things in order, said Ross Buchan, assistant professor of molecular and cellular biology and a member of the BIO5 Institute. These aggregates could possibly be toxic because they are trapping other useful molecules and not letting them do their job.

Buchan and his team set out to investigate how healthy cells clear harmful aggregates from the cell.

What they found was that the aggregates were being removed via endocytosis, which was surprising for two reasons. First, the textbook definition of endocytosis is a process in which proteins, nutrients and chemical signals from outside the cell are brought inside to be degraded and recycled by the lysosome. But in this case, endocytosis was working on aggregates that were already inside the cell. And second, theres already a mechanism, called autophagy, in place for recycling junk that originated from within a cell, yet endocytosis was doing what autophagy should have been doing instead.

Autophagy and also likely, although its still uncertain, endocytosis often slows as we age, and there are genes that are mutated in that pathway that are associated with some neurodegenerative diseases. So people thought the reason aggregates form when we get old, or when you have these diseases, is because that pathway isnt working very well, Buchan said.

Additionally, the accumulation of aggregates slows the endocytosis pathway further, creating a negative feedback loop within the cell.

If we genetically or chemically impede the pathway, then the TDP-43 protein accumulates and becomes super toxic. The cool thing, as far as a therapy for ALS is concerned, is that we can also do the reverse, Buchan said. We can make the endocytosis pathway work better by over-expressing parts of it, like putting the gas pedal down so it goes really fast. When we do that, then the TDP-43 aggregates are cleared really efficiently and its no longer toxic.

Many of the papers experiments were performed in yeast cells, but the general findings are likely translatable to human cells based on initial findings. Buchan called yeast a powerful genetic tool, for understanding cellular processes, including those in human disease.

While the results from Buchans lab are unexpected If I were to pull a textbook off the self, it would say endocytosis is for things that are outside the cell, not inside, so its still pretty heretical, he said there are other labs with data suggesting endocytosis can also clear already internalized proteins.

The next step is to determine how TPD-43 and FUS enter the endocytic pathway, and then to develop ways to make endocytosis work better in these cells.

There are genetic ways to do that, but not chemically at the moment, Buchan said. We think if we have a drug that inhibits the negative regulators of endocytosis, the pathway will go faster as a result. We have a couple ideas of where to start next.

The findings were published in the journal Molecular and Cellular Biology. Buchans co-authors include undergraduate Amanda Warner, former post-doctoral fellow Guangbo Liu, graduate student Aaron Byrd, former graduate student Fen Pei, assistant research scientist Eman Basha and former lab technician Allison Buchanan.

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Pedal to the Metal: Speeding Up Treatments for ALS - UANews