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Cell Biology

Will baldness soon be a thing of the past? – San Bernardino County Sun

Despair not, ye men and women with ever-thinning pates: The follicles on your bald, shiny scalps arent dead. Theyre just, sort of, sleeping.

Researchers at UC Irvine liken those follicles to a sea of 3D printers, just waiting for the command to power up. And theyve figured out how to issue that command, recently micro-injecting a protein that sounds a bit like Scooby Doo into mice.

Our results identify SCUBE3 as a hair-growth activator, says their paper, published recently in the journal Developmental Cell. When microinjected for 4 days recombinant human SCUBE3 induced significant hair growth in mouse back skin.

Not only did SCUBE3 wake up dormant follicles to grow mouse fur, it also worked to grow human hair that was grafted onto the mice. Given time, that human hair could grow (and grow, and grow) longer than the mouses own fur would grow; longer than the mouses body, longer than the mouses tail.

The results were very promising, said Yingzi Liu, one of the researchers.

If youre envisioning a mouse with a Farrah Fawcett do, youre not alone.More than 50 percent of women experience balding, according to the American Hair Loss Association, and by age 50 about 85 percent of men are balding as well.

There are but two medications that treat or stave off hair loss: finasteride (Propecia, Proscar) and minoxidil (Rogaine, Ioniten). It can take at least 6 months for either treatment to start showing results. Theres a long road ahead before SCUBE3 can be tested on people, but the researchers have applied for a patent and hope to get to clinical trials in the next five or so years.

Scientists really care not only that things work, but how they work, said Maksim Plikus, professor of developmental and cell biology and a study author. Right now, were focusing on a deep dive into the mechanisms. But we are excited to the level that we filed for a patent. And were thinking that it has potential for people.

The issue here is dysfunctional signaling, he said. Stem cells for hibernating follicles arent disappearing; theyre just extremely dormant because theyre not getting the message that they should perform.

Questions to be explored next include efficacy and safety. SCUBE3 is a naturally occurring molecule, Plikus said, but how much can be delivered without seeing side effects? How much is too much?

Plikus lab studies how complex tissues and organs regenerate under normal conditions and in response to injury or disease. It aims to understand the nature of stem cell regulatory networks and regenerative behavior in response to organ injury.

Our ongoing work shows that the regenerative abilities of adult mammalian skin are far greater than previously thought, the Plikus labs web site says. In the center of large skin wounds cells can acquire an embryonic-like state and develop new, fully functioning hair follicles. Collectively, regenerative events can be so efficient that several months after wounding, scar tissue can hardly be distinguished from the normal skin.

Further research will be conducted in the Plikus lab and at Amplifica Holdings Group Inc., a biotechnology company co-founded by Plikus.The study team included health professionals and academics from UCI, San Diego, China, Japan, Korea and Taiwan.

The work was supported by grants from the LEO Foundation, Chan Zuckerberg Initiative, W.M. Keck Foundation, National Science Foundation, National Institutes of Health, Simons Foundation, National Natural Science Foundation of China and Taiwans Ministry of Science and Technology.

And, in case youre wondering: Plikus and Liu have thick, healthy heads of hair!

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Will baldness soon be a thing of the past? - San Bernardino County Sun

Cell Biology

Renewal Bio Acquires Breakthrough Stem Cell Technology With Applications in Infertility and Longevity – Benzinga

Renewal Bio, a newly formed biotechnology company focused on infertility and longevity, today announced it has acquired an exclusive license from Yeda Research and Development Co Ltd, the commercial arm of the Weizmann Institute of Science, to a newly developed synthetic embryo technology. The technology was spearheaded by Prof. Jacob Hanna, Ph.D., M.D., as recently published in Cell, and builds on his research published in Nature last year. Renewal Bio plans to develop a bio platform that combines biology, hardware, and software to drive advancements and develop therapies for infertility, genetic diseases, lab-grown organs, and blood system rejuvenation.

The Problem: Humanity is Getting Older and Sicker

Since the turn of the century, developed nations have seen a clear trend: declining birth rates and fast aging populations. With significant socioeconomic implications, this trend threatens to upend health systems, retirement programs, and workforces across the globe. At the beginning of life, this is shown by a 5-10% increase in infertility treatments by U.S. couples each year. Towards the end of life, these issues are manifesting in fast-aging populations that balloon healthcare costs. In the U.S., the aging population is driving national health expenditures to increase at a rate of 5.5% per year, and are expected to reach more than $6 trillion annually by 2027.

The Solution: A Bio Platform to Renew Humanity

To solve these complex and compounding issues, Renewal Bio aims to make humanity younger and healthier by leveraging the power of the new stem cell technology. The technology can be applied to a wide variety of human ailments including infertility, genetic diseases, and longevity.

Renewal Bio's founding team includes:

Anyone interested in joining the company's mission of making humanity younger and healthier can learn more at renewal.bio.

About Renewal Bio

Founded in 2022, Renewal Bio mission is to renew humanity - making us younger and healthier. The company was founded by Omri Amirav Drory and Jacob Hanna to develop therapies ranging from infertility treatments to lab-grown organs using novel stem cell technology developed at the Weizmann Institute of Science. Learn more at renewal.bio.

About Yeda

Yeda Research and Development Company Ltd. is the commercial arm of the Weizmann Institute of Science. Yeda currently manages approximately 500 unique patent families and has generated the highest income per researcher compared to any other academic technology transfer operation worldwide. Through the years, Yeda has contributed to the commercialization of a number of groundbreaking therapies, such as Copaxone, Rebif, Tookad, Erbitux, Vectibix, Protrazza, Humira, and the CAR-T cancer therapy Yescarta. For more information, visit http://www.yedarnd.com/.

About the Weizmann Institute of Science

The Weizmann Institute of Science in Israel is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, Weizmann Institute's scientists are advancing research on the human brain, artificial intelligence, computer science and encryption, astrophysics and particle physics, and are tackling diseases such as cancer, while also addressing climate change through environmental, ocean, and plant sciences.

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Renewal Bio Acquires Breakthrough Stem Cell Technology With Applications in Infertility and Longevity - Benzinga

Cell Biology

Berkeley Lights and the Jaime Leandro Foundation Announce the Discovery, Functional Characterization, and Recovery of a Patient-Derived T cell…

EMERYVILLE, Calif., Aug. 4, 2022 /PRNewswire/ -- Berkeley Lights, Inc. (Nasdaq: BLI), a leader in digital cell biology, and the Jaime Leandro Foundation for Therapeutic Cancer Vaccines (JLF), today announced the discovery, functional characterization, and recovery of a patient-derived T cell receptor sequence against a cancer neoantigen.

Together, Berkeley Lights and JLF were able to measure and identify T cells that were reactive against peptides used in a cancer vaccine that was administered to a patient to successfully stimulate an immune response against their advanced-stage pancreatic cancer leading to complete remission. The patient was treated under the supervision of physicians at Washington University in St. Louis.

The unprecedented speed of these results relied on the Berkeley Lights Beacon system. Applying the cell therapy development workflow, thousands of phenotypic measurements of single T cells were performed within one week. These measurements identified T cells that were cytotoxic and capable of secreting cytokines in response to antigen encounter, which were therefore predicted to be functional and subsequently sequenced at a single cell level. Cloning these T cell receptor sequences and expressing them in nave T cells enabled functional validation against an antigen of interest. This function-first measurement capability of the Berkeley Lights platform is a significant differentiator compared to frequency-based assessments of TCRs which result in functional validation bottlenecks, adding to a growing number of highly differentiated service offerings at Berkeley Lights.

"This unique workflow combines Berkeley Lights' core strength of functional analysis of live cells, along with the use of the new Biofoundry services organization to help customers accelerate their therapeutic discoveries in a faster, more scalable way," said Siddhartha Kadia, Ph.D., chief executive officer of Berkeley Lights. "We look forward to continuing to work with JLF and their partners in evaluating immune response to cancer vaccines, mapping TCRs to neoantigens and ultimately supporting this important work to save patient lives."

The JLF has the mission of providing personalized neoantigen cancer vaccines for appropriate patients who have advanced cancers and seek compassionate use treatment.

"The data is exceedingly clear that, together, we have successfully identified a functional, patient- and antigen-specific TCR validating both our treatment methodology and the Berkeley Lights technology for personalized cancer vaccines compared to conventional approaches," said William Hoos, president of the Jaime Leandro Foundation for Therapeutic Cancer Vaccines. "This is an exciting advancement in our mission."

From the clinical team, Dr. William Gillanders, professor of surgery at Washington University School of Medicine, commented:

"The Berkeley Lights technology can take immune monitoring to the next level by evaluating multiple quantitative measurements of live cell behavior and recover that cell for molecular characterization. This is going to be tremendously useful for the field by providing a much deeper dataset to further understand cancer vaccines and predict clinical outcomes as well as to serve the growing need of combination therapies where TCR-T can be utilized."

1Daniel A King, Amber R Smith, Gino Pineda, et al. Complete remission in a patient with widely metastatic HER2-amplified pancreatic adenocarcinoma following multimodal therapy informed by tumor sequencing and organoid profiling. medRxiv 2021.12.16.21267326; doi: https://doi.org/10.1101/2021.12.16.21267326

About Berkeley Lights

Berkeley Lights is a leading digital cell biology company focused on enabling and accelerating the rapid development and commercialization of biotherapeutics and other cell-based products for our customers. The Berkeley Lights Platform captures deep phenotypic, functional, and genotypic information for thousands of single cells in parallel and can also deliver the live biology customers desire in the form of the best cells. Our platform is a fully integrated, end-to-end solution, comprising proprietary consumables, including our OptoSelect chips and reagent kits, advanced automation systems, and application software. We developed the Berkeley Lights Platform to provide the most advanced environment for rapid functional characterization of single cells at scale, the goal of which is to establish an industry standard for our customers throughout their cell-based product value chain.

Berkeley Lights' Beacon and Lightning systems and Culture Station instrument are FOR RESEARCH USE ONLY. Not for use in diagnostic procedures.

Forward-Looking Statements

To the extent that statements contained in this press release are not descriptions of historical facts regarding Berkeley Lights or its products, they are forward-looking statements reflecting the current beliefs and expectations of management. Such forward-looking statements involve substantial known and unknown risks and uncertainties that relate to future events, and actual results and product performance could differ significantly from those expressed or implied by the forward-looking statements. Berkeley Lights undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties relating to the Company's growth and continual evolution see the statements in the "Risk Factors" sections, and elsewhere, in our filings with the U.S. Securities and Exchange Commission.

SOURCE Berkeley Lights, Inc.

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Berkeley Lights and the Jaime Leandro Foundation Announce the Discovery, Functional Characterization, and Recovery of a Patient-Derived T cell...

Cell Biology

Research Fellow, Mechanobiology Institute job with NATIONAL UNIVERSITY OF SINGAPORE | 303772 – Times Higher Education

Job Description

We are looking for a Postdoctoral Fellow with research experiences in Cell Biology or related Biomedical Sciences field. Relevant research areas include cell-cell junctions, cell signalling, cytoskeletal dynamics or related areas in mechanobiology. The successful candidate will lead a research project on the application of optogenetics to study adhesion proteins and cytoskeletons using advanced microscopy and molecular cell biology techniques.

Our laboratory is based at the Mechanobiology Institute (MBI), National University of Singapore (NUS). We are well equipped with state-of-the-art equipment and integrated core facilities support (microscopy, micro/nano-fabrication, protein expression and cloning, IT) as well as a vibrant and highly collaborative environment based on an Open Lab concept.

Compensation is internationally competitive and commensurate with experiences.

For more information, please visit our lab web site athttps://www.nanoscalemechanobiology.org

Qualifications

Candidates must have a Ph.D. degree in biology or related biomedical fields and outstanding publication record in relevant topics. Proficiency in mammalian cell biology, molecular biology, biochemistry, and live-cell fluorescence microscopy are desirable.

Covid-19 Message

At NUS, the health and safety of our staff and students are one of our utmost priorities, and COVID-vaccination supports our commitment to ensure the safety of our community and to make NUS as safe and welcoming as possible. Many of our roles require a significant amount of physical interactions with students/staff/public members. Even for job roles that may be performed remotely, there will be instances where on-campus presence is required.

Taking into consideration the health and well-being of our staff and students and to better protect everyone in the campus, applicants are strongly encouraged to have themselves fully COVID-19 vaccinated to secure successful employment with NUS.

More Information

Location: Kent Ridge CampusOrganization: Mechanobiology InstituteDepartment : ResearchEmployee Referral Eligible: NoJob requisition ID : 16760

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Research Fellow, Mechanobiology Institute job with NATIONAL UNIVERSITY OF SINGAPORE | 303772 - Times Higher Education

Cell Biology

Maryland Today | Insight From an Inside-out Fruit – Maryland Today

As global temperatures rise and populations of bees and other pollinators dwindle, food crop production is increasingly becoming a puzzle for growers.

A new study by researchers at the University of Maryland puts some of the pieces together, providing insight into exactly how flowering plants develop fruits and seeds.

Understanding this process is especially important because common food cropssuch as peanuts, corn, rice and strawberriesare all fruits and seeds derived from flowers, said Zhongchi Liu, the studys senior author and a professor in the Department of Cell Biology and Molecular Genetics and affiliate professor in the Department of Plant Sciences and Landscape Architecture. Knowing how plants 'decide' to turn part of their flowers into fruit and seed is crucial to agriculture and our food supply.

Funded by the National Science Foundation, the study was publishedlast month in the journal Nature Communications. Liu and her team aimed to discover how fertilizationor pollinationtriggers a flowering plant to start the fruit development process. The team suspected that an internal communication system was responsible for signaling the plant to develop fruit, but the researchers were unsure how that system was being activated by fertilization or pollination.

To find out, the team simulated pollination and fruit development mechanisms using strawberry plants. Strawberries are particularly suited to fertilization modeling due to their unique structure and seed location.

As an inside-out fruit, strawberry seeds are much easier to manipulate and observe than the seeds of other fruits like tomatoes, Liu said. This made it easier for us to view the seeds and extract genetic information from them at multiple stages of plant development.

Liu and her team identified AGL62, a gene universally found in all flowering plants, as the trigger to a plants production of fruit and seed.

AGL62 stimulates the production of an essential plant growth hormone called auxin. Once the gene activates, auxin is synthesized to prompt the creation of seedcoat, the outer protective layer of a seed; the endosperm, the part of a seed that provides food for a developing plant embryo; and fruit. Auxins role in regulating endosperm growth is especially significant for researchers as it impacts the size of the grain and enlargement of the fruit.

Auxin levels can limit how big an endosperm can grow and how much nutrition endosperm can accumulate for a plant embryo, Liu said. More auxin can boost grain size and stimulate fruit enlargement. When theres less auxin, endosperms are unable to feed plant embryos properly and we end up with lowered crop productivitysmaller or deformed fruits that arent commercially viable.

Gerald Schoenknecht, a program director in NSFs Division of Integrative Organismal Systems, added, Strawberry fruits are textbook examples of how the plant hormone auxin produced in seeds controls fruit size. Discovering a gene that is required for auxin synthesis after fertilization may open avenues to achieve fruit development without fertilization.

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Maryland Today | Insight From an Inside-out Fruit - Maryland Today

Cell Biology

Glycan shield of the ebolavirus envelope glycoprotein GP | Communications Biology – Nature.com

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Glycan shield of the ebolavirus envelope glycoprotein GP | Communications Biology - Nature.com

Cell Biology

Associate Professor / Professor of Cancer Biology job with UNIVERSITY OF SOUTHAMPTON | 303905 – Times Higher Education

Cancer Sciences

Location: Southampton General HospitalSalary: 53,353 to 99,330Full Time PermanentClosing Date: Thursday 01 September 2022Interview Date: To be confirmedReference: 1928122CM

Associate Professor Salary: 53,353 67,060 per annum recruitment package will be commensurate with qualifications and experience (Level 6)

Professor Salary: Competitive from 70,119 per annum recruitment package will be commensurate with qualifications and experience (Level 7)

The University of Southampton seeks to recruit a new Associate Professor or Professor of Cancer Biology to expand our existing programmes and track record in this area, ideally in the field of lymphoid malignancy.

Over the last 30 years, our collaborative research teams, based on a single hospital site, have made important contributions to the study of normal and malignant lymphoid biology. Our research has helped transform the understanding and treatment of the most common adult leukaemia, Chronic Lymphocytic Leukaemia (CLL). Our discovery of two distinct CLL subsets has given clinicians and patients a much clearer indication of the likely disease course and has inspired the development of novel therapeutics. In parallel, our observations have driven major advances in lymphoma care, leading to the development and standardisation of effective new antibody treatments and optimal drug regimens (e.g. antibodies that target the CD20 protein). Through our leadership of international clinical trials, we have transformed the standard of care for different lymphoid malignancies (e.g. Hodgkin and Burkitt lymphoma) in the UK and internationally, affecting all stages of patient experience from diagnosis to treatment.

We now wish to further strengthen this area of our research with additional expertise in the fundamental biology of lymphoid malignancy. For the Professorial appointment, we seek an experienced and internationally recognised candidate with outstanding credentials in the field, someone with proven experience who will be attracted to a role in Southampton by our record in B cell biology and cancer immunology/immunotherapy, and our proven capabilities in clinical translation, taking results from the laboratory directly to patients. At the Associate Professor level, we would like to attract a rising star, with the potential, evidenced by early indicators, to become an international scientific leader of the future.

Successful candidates at both Associate Professor and Professor level will have a developing, or strong international profile in the molecular and cellular biology of cancer, respectively, and add synergy and/or a new dimension to our research activities. The successful individual will join a passionate team of basic and translational scientists working in close collaboration with clinical colleagues in our Biomedical Campus at Southampton General Hospital, in purpose-built laboratories in the Somers Building and the Centre for Cancer Immunology. Our work is under-pinned by multiple programme and accelerator awards from Cancer Research UK (CRUK), and houses a CRUK Centre, a CRUK/NIHR Experimental Cancer Medicine Centre, and a CRUK Clinical Trials Unit. Successful candidates at the Professorial level will also have senior research leadership experience and a more established track record of attracting substantive external research funding from research councils, charities and the commercial sector.

More than 250 researchers, clinicians and associated staff focus on all aspects of cancer research, with particular focus on cancer immunology/immunotherapy, cell biology and engineering antibodies to generate therapeutics. Through close interactions of our researchers with the clinical trials unit,we bring ideas and discoveries made in the laboratory into clinical practice as rapidly as possible and ensure that the mechanisms underlying cancer treatments are understood.

We welcome applications from all candidates with an interest in the role, and those who are committed to helping us create an inclusive work environment. We especially encourage applications from candidates from Black, Asian and Minority Ethnic communities, people who identify as LGBTQ+ and people with disabilities.

For further details about the post you are invited to contact the Head of School, Professor Jonathan Strefford jcs@soton.ac.uk

You should submit your completed online application form at https://jobs.soton.ac.uk. The application deadline will be midnight on the closing date stated above. Please submit details for 3 referees and include your CV and publication list with your application. If you need any assistance, please call Lauren Ward (Recruitment Team) on +44 (0) 23 8059 2750, or email recruitment@soton.ac.uk. Please quote reference 1928122CM on all correspondence.

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Associate Professor / Professor of Cancer Biology job with UNIVERSITY OF SOUTHAMPTON | 303905 - Times Higher Education

Cell Biology

NeuroVoices: Ralph Nixon, MD, PhD, on Autolysosome Acidification in Alzheimer Disease and Changing Perceptions of Amyloid – Neurology Live

Despite the billions of dollars poured into developing therapies for Alzheimer disease (AD), little regulatory success has been achieved, with a list of failed or discontinued agents that has continued to grow. A popular approach has been to target amyloid- plaques; however, some in the field argue that this does not result in the intended sustained disease-modifying effects. Most notably, the 2021 FDA approval of aducanumab (Aduhelm; Biogen), an antiamyloid medication, sparked discussion as to whether these drugs are worth the investment.

Led by researchers at NYU Grossman School of Medicine and the Nathan Kline Institute, a newly published paper in Nature continues to challenge the traditional approaches to AD drug development. The latest study findings argue instead that neuronal damage characteristic of AD takes root inside cells and well before these thread-like amyloid plaques fully form and clump together in the brain. Using AD mouse models in vivo, investigators identified small sacs inside cells that were filled with acidic enzymes involved in the routine breakdown, removal, and recycling of metabolic waste from everyday cell reactions, as well as from disease.

In an interview with NeurologyLive, senior investigator Ralph Nixon, MD, PhD, provided in-depth detail on the findings observed and the specific underlying processes taking place. Nixon, a professor of psychiatry and cell biology at NYU Langone, sat down as part of a new iteration of NeuroVoices, and discussed the reasons why the community should seriously consider changing their perceptions on amyloid-, AD drug development, and the root causes of the disease.

Ralph Nixon, MD, PhD: As the audience knows well, Alzheimer disease is a disorder where toxic proteins accumulate in the brain and ultimately kill neurons and cause cognitive decline. Weve been interested in the mechanisms in neurons for clearing these types of proteins since it lives for the life of the individual. This process must be efficient for the cell to survive for that long. One of the principal ways that clearance takes place is the process of autophagy. It basically is 2 steps. One, to sequester unneeded or obsolete or damaged proteins, especially as they accumulate in aging and stress, and to deliver them to a lysosome, which is the digestive compartment of the cell, filled with dozens of digestive enzymes of various sorts. The fusion of that with the sequestered material in that vesicle is followed by acidifying the compartment, because the lysosome is highly acidic. In order for these proteases and hydrolases to work, that acidification takes place upon fusion, and then the process of digestion occurs, hopefully, if it's successful, to completely digest the contents. This is an area that we've been investigating for a long time, and mostly, initially in human brain. Over the years, we've documented what appears to be a unique degree of pathology of this system, the autophagy system, and the lysosomal dysfunction. The degree seemed to us to be unique among all the different age-related disorders.

Another feature was that amyloid- and metabolites of APP [amyloid precursor protein] were accumulating in these autophagy vacuoles, which are the packets of waste that accumulate. We thought that there was a close connection between autophagy failure and the accumulation of amyloid and other things. The goal at that point was to track this process in mouse models, where we could look at the very earliest stages, we knew in a genetically identical model that had a mutation of Alzheimer disease so that we could know that these mice are going to develop pathology. We could follow that evolution from the beginning to the end stages of the process. This was difficult to do because there were no tools available that were really reliable.

We decided to construct a mouse model in which we transgenically introduced a protein that is a marker of the autophagic vacuoles, and in particular, auto phagosomes. That construct was tagged with two fluorescent probes, a red and a green probe. The concept behind it is that once it attaches to the first stage of autophagy, sequestration, we can follow the whole efficiency and progress of that pathway all the way from sequestration to clearance. In addition, the dual fluorescence allowed us to track the pH (potential hydrogen) of the compartments because this turns out to be the key change that allows us to identify the vesicles. As digestion occurs, the color of the fluorescence turns from yellow to red, which indicates successful fusion of the lysosome and digestion of the materials. To introduce this particular construct into a mouse that was also engineered to have mutations that mimic certain aspects of Alzheimer's disease pathology, we could then follow the progress of autophagy and its disruption during the evolution of the disease, and as before the onset of anything that was previously associated with Alzheimer's, and then to all of the consequences of any disruption that occurred. This worked out beyond our dreams as to how successful we could reveal pathology that had not been seen before.

There were a bunch of surprises, but one of the things we were most interested in and were able to confirm is that the very first thing that happens in a in these mice is an abnormality of the lysosome. The lysosomes start to lose the ability to acidify. We know why that happens now, but the important thing is that this was happening very, very early before any manifestations of the Alzheimer process that most people track, ie, amyloid outside the cell, plaques, and cytoskeleton changes. This is the first thing that we can detect during this Alzheimer evolution in these mice.

The other interesting thing is that amyloid- and other metabolites that we consider toxic in Alzheimer's disease, one of them ill call C99, are the first cleavage of APP to generate this c-terminal fragment. We sometimes call it CTF, or call it C99. That then gets cleaved to amyloid-. It's been one of these molecules that has a lot of interesting toxicities and has been generally ignored in the amyloid cascade hypothesis because the focus has been exclusively on amyloid-. These molecules are accumulating along with other waste in the affected neurons in this mouse model. There was a close connection there between the earliest changes, and even earlier changes in lysosomes than in the amyloid, that is considered to be the earliest stage of disease.

The biggest surprises were some other things that the probe was able to reveal. One of which is that this failure of autophagy resulted in massive accumulation of waste vesicles in the cells, so much so that they are pushing the circumference of the cell body, of the neuron, and causing these balloon-like blebs that are deeply fluorescent because they're basically packed with autophagy waste. They're all around the surface of the cell, which made it look like a flower. That was the source of the description of these phenomena as PANTHOS. P for poison and anthos, the Greek word for flower.

This process, to our knowledge, has never been described. The probe allowed us to see it. In addition to that process, the accumulation of these waste artifact vacuoles was encroaching on the center of the cell and transformed, coalesced into this network of membrane tubules that actually had fibrils of amyloid. Again, this was something that to my knowledge had never been visualized: an intact cell that's still alive accumulates the amyloid that's normally just associated it with the outside of the cell. If you had just stayed within amyloid, you would think this is a plaque. But in fact, it's an intact cell that has all the features of an amyloid plaque within it but is still alive.

The other important piece of information is that all the plaques that develop in these mouse models originated from the death of these PANTHO cells, or PANTHOS neurons. Once the cell dies, the ghost becomes the plaque outside the cell. The bottom line here, and one of the main messages, is the importance of lysosome dysfunction at the earliest possible stage of Alzheimer. This connects with the genetics that we now know. That C99 that I mentioned earlier, the APP fragment, we now know, inhibits the acidification process. When it accumulates, it actually sets a vicious cycle to further de-acidify the lysosome. The lysosome is genetically and pathologically at the earliest outset of evolution at the least in amyloid- models.

The other thing that was important in terms of the clinical relevance, is that, as many people know, to this point, the vaccines for amyloid have not been very successful. When you think of what the sequence is that we've defined, it's an inside-out process rather than the cascade hypothesis that the lesion and the amyloid outside is killing the cell as a secondary process. In the case of if we are correct, which I think the pathology speaks for itself, there's very little logic in removing the amyloid on the outside because the cell has already, you know, been so compromised, that it's going to die. There's no reason to remove the amyloid on the outside because it originated from basically a dying cell. One has to now attack the process inside the cell, and to target these individual processes, lysosomes or whatever other autophagy dysfunction that you can reverse, and to cure the cell from inside route rather than by removing amyloid. This is a paradigm shift. Of course, so far, we haven't heard a response from many in the amyloid vaccine field, I'm sure there'll be still some people that will say, well, we need more work, which of course, we do.

Transcript edited for clarity. Click here for more NeuroVoices

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NeuroVoices: Ralph Nixon, MD, PhD, on Autolysosome Acidification in Alzheimer Disease and Changing Perceptions of Amyloid - Neurology Live

Cell Biology

Research Assistant Cellimage Project, College of Medicine, (NUIG RES 199-22) job with NATIONAL UNIVERSITY OF IRELAND, GALWAY | 303808 – Times Higher…

Research Assistant Cellimage Project

Regenerative Medicine Institute, College of Medicine

NUIG RES 199-22

Information on project/centre

The Regenerative Medicine Institute (REMEDI) is a world-class biomedical research centre which focuses on research in cell and gene therapies to address a number of major disease targets. Our research spans a broad spectrum of translational strategies including basic stem cell biology, advanced manufacturing, contemporary analytics and clinical trials.

The CELLIMAGE Project, funded under the Disruptive Technologies innovation fund is designed to develop novel artificial intelligence tools to support next generation cell therapy manufacturing. The project is a partnership between REMEDI, Valitacell Ltd., and Intel.

Job Description:

Duties:

Employment permit restrictions apply for this category of post

Salary: 27.874 30,742 per annum

Continuing Professional Development/Training:

Researchers at NUI Galway are encouraged to avail of a range of training and development opportunities designed to support their personal career development plans.

Further information on research and working at NUI Galway is available on Research at NUI Galway

For information on moving to Ireland please see http://www.euraxess.ie

Further information about NUI Galway School of Medicine is available at this link.

Informal enquiries concerning the post may be made to Professor Frank Barry at frank.barry@nuigalway.ie

To Apply:

Applications to include a covering letter, CV, and the contact details of three referees should be sent, via e-mail (in word or PDF only) to Ms. Amy Hogan amy.hogan@nuigalway.ie

Please put reference number NUIG RES 199-22 in subject line of e-mail application.

Closing date for receipt of applications is 5.00 pm 16/08/2022

We reserve the right to re-advertise or extend the closing date for this post.

National University of Ireland, Galway is an equal opportunities employer.

All positions are recruited in line with Open, Transparent, Merit (OTM) and Competency based recruitment

'NUI Galway provides continuing professional development supports for all researchers seeking to build their own career pathways either within or beyond academia. Researchers are encouraged to engage with our Researcher Development Centre (RDC) upon commencing employment - see http://www.nuigalway.ie/rdc for further information.'

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Research Assistant Cellimage Project, College of Medicine, (NUIG RES 199-22) job with NATIONAL UNIVERSITY OF IRELAND, GALWAY | 303808 - Times Higher...

Cell Biology

These sterile mice have been modified to make rat sperm – Popular Science

Biologists have successfully engineered animals that produce the sperm of a different species, which brings labs one step closer to animal reproduction that uses nothing but the animals DNA. And while theres potential to rebuild endangered species populations, or even bring extinct species back to life, dont worryJurassic Park will probably stay fiction.

The new research published today in Stem Cell Reports has demonstrated that it is possible to produce rat sperm in sterile hybrid mice. While the technique still needs to be fine-tuned, the study authors say that their approach of adding engineered stem cells from one species to embryos of another species, called blastocyst complementation, has the potential to boost endangered species. If at-risk species arent able to maintain healthy numbers, generating their eggs and sperm in a lab could be used as a new tool to build populations up.

The teams process used stem cells, specifically pluripotent stem cells. Stem cells are the raw materials that make all kinds of cells, but the pluripotent stem cells can produce the greatest number of different cell types. These stem cells naturally develop only in embryos, but its also possible for other types of cells, such as those from a regular tissue sample, to be transformed into pluripotent stem cells. So this gives scientists a more readily available source to brew these stem cells in the lab. Adding them to the sterile embryos of a different living animal ultimately converts these stem cells into germ cells, such as sperm or eggs.

Previous research had already shown that rat sperm could be made in mice using pluripotent stem cells, says Ori Bar-Nur, a biologist at the Swiss university ETH Zurich and a coauthor of the study. The process involves creating a chimera, which is an artificial genetic hybrid of multiple animalsin this case, mice and rats. But past experiments with rat-mice chimera produced mouse sperm in addition to rat, resulting in a mix that was difficult to distinguish, isolate, and use. Unlike these past experiments, Bar-Nur and his team used mice that were genetically sterile. By adding the pluripotent stem cells of a rat to a sterile mouse embryo at a particular stage in its development (in this case the blastocyst stage) only the rats sperm formed in the resulting rat-mouse chimera.

Its removed a hurdle, especially if the process can work with other species, says Kevin Gonzales, a postdoctoral stem cell biology researcher at the Rockefeller University who was not involved with the study.

This new system wasnt a perfect success, though. The sperm produced by the chimeras could fertilize rat eggs, but at a relatively low rate, and the resulting embryos didnt develop into live offspring. Bar-Nur and his team arent sure why this is, but they suggest that it could be because the cells had been frozen and thawed, which is known to reduce viability. Its something we still need to pursue and are working on, Bar-Nur says.

Still, Gonzales says that the teams ability to engineer a chimera that exclusively produced the sperm of a different species shows promising progress for the future of stem cell propagation in conservation efforts. Continuing down this line of research has the potential to repopulate endangered (or even extinct) species with dwindling numbers. Small populations lead to a dangerous lack of genetic diversity, which increases the risk of extinction. If you think about critically endangered species, you probably wont have access to spermatozoa, explains Bar-Nur. But you might have tissue samples, and if we could transform that into pluripotent stem cells and find an evolutionarily close species, we could potentially, eventually, repopulate the species.

[Related: Airborne animal DNA could help biologists track endangered species]

There are a number of steps left before this technology can be put to practical use. First, biologists have yet to actually develop a living creature with sperm made from this particular type of stem cell propagation, blastocyst complementation. Additionally, no one has been able to produce female eggs with this method. However, both Bar-Nur and Gonzales say theres every reason to think its possible.

Gonzales points out that future use of the application will depend on having or making pluripotent stem cells. Samples of endangered species tissue are being collected and preserved, so labs could gain access, he says. However, the specific set of genetic keys needed to transform cells into pluripotent stem cells varies from species to species. The DNA sequences of lab mice, for instance, are relatively well known, but those of a rare tiger might not be.

The reproductive systems of mammal species present another barrier: they will need hosts to carry any viable embryos, says Gonzales. Even if sperm and eggs are successfully created and combined, its unknown whether the embryo could healthily develop in the uterus of a different species, even one that is closely related.

So as Jurassic Park-esque as it sounds to use cell samples to bring an extinct species back to lifeor even a nearly-extinct species back from the brinkresearchers still have a few hurdles to overcome before the technology can be put into practice.

More:
These sterile mice have been modified to make rat sperm - Popular Science