Immunology

Italian Government to close all school and universities – Buzz.ie

Italian News Agency, ASNA, has reported today that following a meeting between the Prime Minister Guiseppe Conta and ministers at Palazzo Chigi today, the Italian government is set to close all schools and universities for two weeks.

Northern Italian schools, businesses and universities have been closed for a week now following the coronavirus outbreak resulting in towns in the North of the country going into quarantine.

There have been 2,500 confirmed cases of the virus in Northern Italy, with 79 confirmed deaths, making it the most affected area outside of China.

Professor Kingston Mills, an expert in immunology and the head of the centre for the study of immunology at Trinity College, Dublin, has also come out today to ask the questions of should flights still be running in and out of Italy given the severity of the outbreak. He said; "We need to look more seriously at means of curtailing travel to that region."

Mills, who spoke with RTE's Sean O'Rourke this morning on The Sean O'Rourke Show said he queried the information put out by the HSE saying that the virus could be contracted within 15 minutes of being in the company of someone who has the virus saying, "fifteen minutes is an arbitrary figure".

There has been no evidence so far in Ireland that shows local transmission of the virus, which is slowing the spread of Covid-19 in the country.

Ryanair have also confirmed there has been a notable drop in the number of flight bookings from the middle of March right into next month.

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Italian Government to close all school and universities - Buzz.ie

Physiology

Oakcrest School Advances to States in the Virginia Science Olympiad – Vienna Connection

Oakcrests entire Science Olympiad team. Photo contributed

Oakcrest School earned a spot in the Virginia Science Olympiad high school state tournament by finishing in fifth place at the regional competition held at the University of Mary Washington on Saturday, Feb. 8.

Oakcrest was the only all-girls school among the eleven in the high school competition, which included Thomas Jefferson High School for Science and Technology, Fairfax High School and McLean High School. With two teams in the high school division, Oakcrest took first place among the eleven high schools in the Anatomy and Physiology competition, and fourth in the coding-intensive Detector Building category.

Oakcrest was also the only all-girls school among the thirteen middle schools that competed in the regional tournament. With one team in the middle school division, Oakcrest placed tenth out of twenty teams.

Notable high school student achievements included:

Mackenzie M. (20): First place, Anatomy & Physiology

Rachel F. (22) and Faven K. (23): Second place, Gravity Vehicle

Sofia J. (21) and Hannah L. (21): Fourth place, Detector Building

Rachel F. (22) and Grace C. (22): Sixth place, Fossils

Notable middle school student achievements included:

Vivian K. (25) and Ashleigh Y. (25): Fourth place, Heredity

Megan B. (25) and Maddie M. (26): Sixth place, Density Lab

It was a wonderful team effort across the board. The girls represented Oakcrest very well! said Science Olympiad coach and Oakcrest science teacher Dr. Kat Hussmann.

This will be the second year in a row that Oakcrest sends students to the Virginia Science Olympiad State Tournament. In 2019, Oakcrest was the first ever all-girls team to compete in the state tournament and Dr. Hussmann received the Virginia Science Olympiad Coach of the Year award. States will take place on March 28 at the University of Virginia.

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Oakcrest School Advances to States in the Virginia Science Olympiad - Vienna Connection

Physiology

Fast Talk, ep. 100: Polarized Training – past, present, and future – VeloNews

Dr. Seiler, aka the Jay-Z of physiology, talks about the inception of the polarized method.

Welcome to episode 100 with Dr. Stephen Seiler! We are so proud to have now brought 100 episodes of our passion for the bike to you. Thanks to all of you for coming along with us as weve interviewed some of the best physiologists, nutritionists, and athletes in professional cycling, and many of the most knowledgeable coaches in the world.

Today in episode 100, we get nearly two hours of Dr. Seiler, aka the Jay-Z of physiology. Our conversation is very natural, casual even, but there are so many moments of enlightenment and clarity.

Yes, Trevor wrote an outline for the show, as he always does. Thanks, Trevor. Then we proceeded to completely disregard it.

In many ways, it makes for a heck of a good show. We learn about the inception of the polarized method, from the creator himself. We discuss Dr. Seilers current research on the all-important aerobic threshold. And we jawthats my nod to his Texas rootsabout the future of sport science. Get ready for the wisdom to drop.

Are you following Dr. Seiler on Twitter? If not, you should. He frequently posts workout challenges, surveys, and his commentary on new scientific research and studies.

Now, sit back and grab your favorite beverage, or, better yet, find a nice long stretch of lonely road to listen in. Lets make you fast!

Check out all 100 Fast Talk Podcast episodes here.

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Fast Talk, ep. 100: Polarized Training - past, present, and future - VeloNews

Physiology

Cooley Strengthens IP Litigation Team With DC Duo – Financial Post

Arriving from Finnegan, they bring powerful life sciences, ANDA litigation capabilities

WASHINGTON Cooley is growing its market-leading intellectual property litigation practice group with the addition of partners Sanya Sukduang and Jonathan Davies, who will be based in Washington, DC. Arriving from Finnegan, Henderson, Farabow, Garrett & Dunner, Sukduangs and Davies practices focus on life sciences with an emphasis on pharmaceuticals litigation, including HatchWaxman Abbreviated New Drug Application (ANDA) litigation.

Sanyas and Jonathans experience navigating complex ANDA cases adds significant depth to the life sciences component of our IP litigation practice and complements the work done by our patent counseling and life sciences partnering practice groups, said Stephen Smith, chair of Cooleys intellectual property litigation practice. Together, their experience will prove an invaluable asset to our clients, particularly the increasing number of them with later-stage products ripe for ANDA litigation.

Sukduang advises clients on patent litigation before federal district courts and the US Court of Appeals for the Federal Circuit, as well as all aspects of proceedings before the Patent Trial and Appeal Board. His work centers on litigating matters concerning ANDA challenges for brand drug manufacturers, diagnostic methods, biological products and medical devices. Sukduang also guides clients on an array of issues concerning biologics, including due diligence investigations and strategic patent portfolio planning. He formerly chaired Finnegans diversity and inclusion committee.

Davies practice centers around patent litigation, particularly on pharmaceutical and biotechnology cases, including HatchWaxman litigation related to ANDAs and biologics litigation under the Biologics Price Competition and Innovation Act. He has deep experience advising on all aspects of pretrial and trial federal district court practice, in addition to advising clients on infringement and validity opinions. Prior to his legal career, Davies completed graduate studies in human physiology and conducted doctoral and post-doctoral research in cellular and molecular biology and genetics.

We know firsthand how high stakes ANDA litigation is for the innovative companies we advise, said Sukduang. We are excited about the opportunities well be able to provide our clients with the support of Cooleys powerful IP litigation platform.

We look forward to delivering successful results for our clients as we team up with our new colleagues, said Davies. We are also impressed by Cooleys standout, collaborative culture and are eager to help build on the firms legacy as it continues to grow.

With a team of 60+ lawyers, Cooleys IP litigation practice is renowned for its ability to win bet-the-company competitor cases in which multibillion-dollar products, technologies and brands are at stake. The practice has unprecedented experience representing clients in tech and life sciences matters. Cooley boasts one of the most active patent litigation practices in the US, having handled 525+ patent cases and 70+ Federal Circuit patent appeals, the vast majority as the appellee, in the past five years.

About Cooley LLP

Clients partner with Cooley on transformative deals, complex IP and regulatory matters, and high-stakes litigation, where innovation meets the law.

Cooley has 1,100+ lawyers across 16 offices in the United States, Asia and Europe.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200303005657/en/

Contacts

Andrea Orzehoski Cooley LLP aorzehoski@cooley.com +1 858 550 6259

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Cooley Strengthens IP Litigation Team With DC Duo - Financial Post

Physiology

Our Education: SIUEs Fernandez del Valle committed to optimizing womens health – Alton Telegraph

SIUEs Maria Fernandez del Valle, PhD, assistant professor of exercise physiology in the School of Education, Health and Human Behaviors Department of Applied Health.

SIUEs Maria Fernandez del Valle, PhD, assistant professor of exercise physiology in the School of Education, Health and Human Behaviors Department of Applied Health.

SIUEs Maria Fernandez del Valle, PhD, assistant professor of exercise physiology in the School of Education, Health and Human Behaviors Department of Applied Health.

SIUEs Maria Fernandez del Valle, PhD, assistant professor of exercise physiology in the School of Education, Health and Human Behaviors Department of Applied Health.

Our Education: SIUEs Fernandez del Valle committed to optimizing womens health

EDWARDSVILLE Southern Illinois University Edwardsvilles Maria Fernandez del Valle, PhD, is researching optimizing womens health.

The assistant professor of exercise physiology in the School of Education, Health and Human Behaviors Department of Applied Health is a prime example of a teacher-scholar who has established multi-disciplinary collaborations and consistently involves students to pursue high impact research.

My research focuses on improving exercise prescription through different lines of study to help individuals optimize their health, she said. Currently, were targeting women, and conducting research on cardiac fat and function to determine how different modes of exercise can help us improve both.

I want to improve the way we prescribe exercise, she said. We need a larger sample size to clearly see data trends, but early indications show that we can have a high impact on cardiac fat around the heart with resistance training alone. The implication then would be that obese women should do resistance training to target more internal fat rather than the fat you see on the outside. Because, internal fat is what I linked to the development of metabolic and cardiac diseases.

Two of her primary collaborators are Jon Klingensmith, PhD, assistant professor in the SIUE School of Engineerings Department of Electrical and Computer Engineering, and Pamela Woodard, PhD, with the Washington University School of Medicine.

Fernandez del Valle is also a research mentor for students, most of whom have earned competitive research awards and Undergraduate Research and Creative Activities accolades.

We can teach in the classroom and explain concepts, but when students are in a lab, I can see their faces and how it just clicks that Oh, now thats what this means and This is connecting with this, she said. Without my collaborators and students assistance, this work would not be possible. It involves human subjects, assessment training and implementation, data reporting and much more.

Before working in this lab, I wasnt sure what I wanted to do post-graduation, said graduate student and research assistant Paige Davis. Now, I know I want to work in a research lab at a college or government agency. I love the mix of human interaction and data entry, and how everything comes together to achieve interesting results.

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Our Education: SIUEs Fernandez del Valle committed to optimizing womens health - Alton Telegraph

Physiology

First-Year Lab Experience Gave This Student the Confidence to Aim for a Ph.D. – UVA Today

A University of Virginia biomedical engineering student is trying to tackle the worlds No. 1 cause of death on a genetic level.

Rita Anane-Wae, from Ghana by way of Glendale, Arizona, and a third-year biomedical engineering student, is using a 2019 Harrison Undergraduate Research grant to seek a genetic solution to atherosclerosis, or the build-up of plaque in ones arteries, which impedes blood flow.

There are cells that will try to fix this problem by covering them and basically pushing the plaque down to allow blood flow, she said. These cells will try to reduce that plaque so that there is correct blood flow. In very serious cases, the plaque can harden and break off. Once it breaks, it can get lodged somewhere and cause a stroke or a heart attack.

Created through a gift from the late David A. Harrison III and his family, the Harrison Undergraduate Research Awards fund outstanding undergraduate research projects. Selected by a faculty review committee, awardees receive as much as $4,000 apiece to pursue their research interests, under the direction of a faculty mentor.

Anane-Wae started working in a laboratory run by Mete Civelek, an assistant professor of biomedical engineering, as a second-year student.

Civelek had already altered her life. Anane-Wae came to UVA to be a chemical engineer. She met Civelek when she signed up as a first-year student for a program that offered faculty mentoring.

At the time I was a chemical engineering major with an interest in biomedical engineering, Anane-Wae said. After talking with him, he was able to assuage my fears about biomedical engineering.

Biomedical engineering is a relatively new field and as such, I did not believe there were many jobs out there, and my parents were worried for the same reason, she said. Mete has a chemical engineering undergrad degree and a masters and Ph.D. in biomedical engineering, so he was the perfect person for me to talk to. He explained the two fields in a unique way, unlike what I had read and seen on YouTube.

Honestly, I love biomedical engineering. When I switched into biomedical engineering, literally in my first class, I though Oh, my God, this is home. I am learning about anatomy, physiology, genes and cells, and it is still all really exciting for me.

Civelek also suggested Anane-Wae participate in the research trip to Uganda through the UVA Minority Health & Health Disparities International Research Training program to perform research on congestive heart failure. While in Uganda, Anane-Wae made rounds with a doctor at a local hospital and met a 17-year-old girl suffering from congestive heart failure.

Her legs were all swollen, Anane-Wae said. She had edema and her stomach was filled with fluid. I was looking at her and thinking, This girl cant lay down because of all the swelling and she cant even be at rest. And I was thinking, She is about my age and I am fortunate enough to be traveling the world and she is here stuck in this hospital bed.

Her encounter with the girl became part inspiration to her and part reminder that congestive heart failure is not just for older patients.

I have a hard time accepting what I am capable of doing, Anane-Wae said. Being here, being in Uganda, working in the lab, it has taught me that I am basically capable of making change. I know what I am supposed to be doing with my time and my future and I know that doing it makes me happy and will make other people better.

In her lab work, Anane-Wae studies a specific gene melanoma inhibitor activity 3, or MIA3 that affects smooth muscle cells.

Smooth muscle cells are able to basically cover the plaque in that disease state, Anane-Wae said. We are running experiments to see how us modulating MIA3 affects the disease.

She said she and members of the research team in the lab also performed experiments knocking out the MIA3 gene from the cells, which led to a more serious disease state.

I think experiments like these are really important because we are not yet at the stage where we can do gene therapy on a person, Anane-Wae said. If you knock out specific genes, it will affect things that we dont understand yet.

Anane-Wae is working on a small section of a large field, but she thinks there is promise in the work she is doing.

The genome-wide association studies show that 161 different genes so far have been associated with coronary artery disease, she said. And we are studying just one. There is so much further that we have to go.

The path is really long, but we are trying to understand the mechanism by which one gene affects the disease and if we actually figure out that mechanism, we can try to apply it to the other genes and maybe understand the bigger picture.

Research can lead her down many blind alleys, which she understands. Anane-Wae is also very conscious of the law of unintended consequences, and how something that solves one problem can create other problems in the process.

We can say that about everything, she said. I think that is the way with all new development. You fix problems and new ones will arise, and then you fix those, too. So we can only do so much. But I think what I have learned is that I have found something about which I am passionate. I have found something that I enjoy and here at UVA, I have found a community of people who will help me develop my skills.

Included in that community, Anane-Wae cited Civelek and Redouane Aherrahrou, an American Heart Association Postdoctoral Fellow with whom she works.

Aherrahrou has known Anane-Wae since she joined the lab in 2018. When she first joined our lab, Rita knew only the fundamental lab skills and methods, he said. After a short amount of training, she learned rapidly and became very familiar with the cell culture techniques and appropriate lab handling. She performed the experiments independently. Her interactions with other lab members are both professional and friendly.

He described Anane-Wae as a diligent researcher, a gifted student, an inspiring person, and enjoyable to be around.

She has a great personality, is open to guidance and responds well to criticism, he said. She wants to apply to Ph.D. programs after she graduates, and I predict a great future in her career as a research scientist.

Civelek said he enjoys having Anane-Wae as part of his team.

She is hard-working, curious and eager to make a scientific impact, he said. I can see the joy in her face when she learns something new. She gets along well with everyone in the lab and is a role model to those who are junior to her. She has a bright future and I am very proud of her accomplishments.

Civelek said Anane-Wae was recently awarded a German Academic Exchange Research Internship in Science and Engineering, which is presented to only 300 students from the U.S. and Canada.

Redouane and Mete both have high standards for me and motivate me to do my very best, Anane-Wae said. They have instilled a confidence in me that I did not have prior to joining the lab, and they continuously push me to achieve great things. I am so fortunate to have these two individuals as mentors, in addition to all of the other members in the laboratory.

A Blue Ridge Scholarship recipient, Anane-Wae is member of the National Society of Black Engineers and the Society of Women Engineers. She also has received a Hugh Bache Scholarship.

Anane-Wae said she is looking at doing big things, such as gene therapy, but realizes that she has to take small steps at first, and that her friends in the lab will help her out when things go wrong.

She has also learned that research is a team effort, not a solo pursuit.

You cant do research by yourself, she said. You wont be able to get anything done. You will have to depend on other people and you have to be able to share what you have learned. You wont get anything done in any amount of time if you dont trust other people and work together.

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First-Year Lab Experience Gave This Student the Confidence to Aim for a Ph.D. - UVA Today

Physiology

660 young scientists invited to 70th anniversary of Lindau Nobel Laureate Meetings – The Medical News

Young scientists from 101 countries are invited to the 70th anniversary of the Lindau Nobel Laureate Meetings. This was the result of the decision taken today by the Council for the Meetings to conclude the nomination and selection process.

"We are pleased to inform you that the scientific review panel of the Meetings has selected you to participate in the 70th Lindau Nobel Laureate Meeting taking place from 28 June to 3 July 2020 in Lindau, Germany." While the "important phone call from Stockholm" usually comes as a complete surprise to freshly selected Nobel Laureates, the young scientists have been waiting for days for this message in their mailbox. - Today the notifications of acceptance are sent from Lindau to the young researchers all over the world.

Countess Bettina Bernadotte, President of the Council: "Every year it is very moving to be able to offer so many excellent students, PhD candidates and post-docs this opportunity for an exchange and for the further development of their careers. For our 70th Meeting we are particularly pleased that we were able to gain new academic partners in four countries who will send Young Scientists to Lindau this summer."

In addition to almost 200 academic partners - academies of science, universities, foundations and research-based companies - once again six Nobel Laureates nominated young scientists for participation. All nominees have gone through a demanding, multi-stage selection process over the past few months: Following the nomination, they had to submit extensive documentation on their previous scientific career as a first step. On this basis a preliminary evaluation took place. For the first time this year, it was supported by Lindau Alumni who had attended the Lindau Meeting themselves in previous years. The final decision was taken by the scientific chairpersons of the 70th Lindau Meeting - this year with an interdisciplinary programme (every five years) professors from three scientific disciplines: Heiner Linke and Wolfgang Lubitz (Chemistry), Klas Krre and Stefan Kaufmann (Physiology or Medicine) as well as Lars Bergstrm and Rainer Blatt (Physics).

Young scientists around the globe interested in participating in future Lindau Nobel Laureate Meetings can obtain information here: http://www.lindau-nobel.org/application-faq (application procedure from September 2020) The 71st Lindau Nobel Laureate Meeting from 27 June - 2 July 2021 will be dedicated to chemistry by rota.

These young scientists will attend the 70th Lindau Nobel Laureate Meeting

- 660 researchers from 101 countries

- 45% female, 54% male, 1% no comment

- youngest participants: 18 years

- Disciplines: 34% Chemistry, 16% Physiology or Medicine, 21% Biology, 29% Physics

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660 young scientists invited to 70th anniversary of Lindau Nobel Laureate Meetings - The Medical News

Cell Biology

‘Cells At Work!’ Will Teach You About Biology, With Gratuitous Violence and an Overload of Cuteness – /FILM

(Welcome toAni-time Ani-where, a regular column dedicated to helping the uninitiated understand and appreciate the world of anime.)

Whenever a piece of entertainment tries to be educational, it usually suffers from one of two things: either it shoves a bunch of facts down your throat to the point where it becomes overwhelming and dull, or it dumbs down the story to appeal to kids or complete newbies to a degree that it alienates the rest of its audience.

Cells at Work! is different. This is an anime that takes the edutaining from Magic School Bus, the anthropomorphized cuteness of Inside Out, and the horror and gory violence of the Anatomy Park episode of Rick and Morty. The premise: we follow the inside of the human body, where cells are depicted as humans really dedicated to their jobs. Our main character is a red blood cell that always gets lost on her way to deliver boxes of oxygen to different locations, and a white blood cell thats really good at slaughtering bacteria (and absolutely loves to kill them). Its a godsend for nerds studying biology, and it basically confirms my belief that deep down, were all anime inside an incredibly violent anime where cells are constantly on the edge of a gruesome and traumatic demise. Ahead of its second season, which is coming later this year, lets revisit an anime thats literally a story about you. Yes, you!

The first thing to note is that Cells at Work! really, really commits to its concept. It reimagines our bodies as a huge metropolis and every tiny cell as a person, which results in incredibly crowded open spaces, a lot of diverse landscapes, and unfathomable amounts of death and destruction.

The cast of the show is huge, and the characterizations are very creative, from macrophages as hardworking cleaning workers (and occasionally brutal and jovial mass murderers), to T-cells as nave young boys without battle experience, to white blood cells as elite combat units and red blood cells as food delivery people. Then theres the shows secret weapon: the platelets, imagined as cute little kindergarteners. Forget about Baby Yoda platelets are not only real, they keep you from bleeding out whenever you get a paper cut, and they are precious babies.

Anime fans may recognize the animation in Cells at Work! as being made by the same studio that gave us Jojos Bizarre Adventure (yes, there are indeed Jojo references in the show). The show includes many, many scenes of gratuitous and colorful anime violence thats not only visually stunning, but they make you appreciate the work your body does in keeping you alive while you spend your time reading this article. All pathogens look like monsters under a microscope, but Cells at Work! blows them out of proportion and imagines a wide variety of creatures that range from kind of cute to outright disturbing, as is the case of a virus looking like a pink hat that takes over cells and turns them into zombies, or a parasite that is depicted as a full-on kaiju.

And it is in this juxtaposition of cuteness and hyper-violence and horror that Cells at Work! thrives. The show has a very tongue-in-cheek tone throughout, fully acknowledging and diving into the ridiculousness of its premise and energetically playing with it. Not only does it manage to teach you about the different cells in your body and how different pathogens affect you, but it does so through goofy comedy that hides the gruesome seriousness of what its portraying, resulting in one of the most entertaining anime in recent years.

By presenting the smallest areas of the human body as massive cities, every single problem becomes an apocalyptic-level catastrophe. A sneeze becomes a rocked being launched into the sky, a cut becomes a nuclear blast that opens a huge hole in the ground, making every small event feel incredibly important. This serves to both educate you on how your body works and reacts to pathogens and to caution about how to prevent things like heatstrokes. It might make you actually care about what happens inside you and maybe even inspire you to take better care of yourself.

Theres no better example of this than episode 7, which deals with cancer. As controversial with some audiences as it was popular with other audiences and even doctors, the episode is perhaps the most somber of the season. Cells at Work! takes the horrible disease and characterizes it as a tragic boy who saw his entire family hunted down by white cells just for being born different, and grew to despise all cells as a result. Though some took issue with how sympathetic the cancer cell seemed to be, the show doesnt try to say anything positive about the disease, but gives the character a tragic backstory in order to reflect the real tragedy that is cancer itself. Cells at Work! may have a very goofy sense of humor, but it isnt afraid to slow down and reflect on how serious some of the threats to the human body really are, as it challenges the notion of what edutainment can be.

Cells at Work! does what Osmosis Jones tried and failed to do: it makes you learn new things without it getting in the way of a fun and cute story of cells going about their day. The show manages to take all the action, blood, and cute little creatures typical in anime and mixes them with actual microbiology lessons.

Whether youre here to learn some basics about how cells work and how pathogens affect the body, or just in it for some very violent, visually inventive action (and also those platelets), Cells at Work! has something for you.

Watch This If You Like: The Magic School Bus, Osmosis Jones, Dr. Stone.

Cells At Work is now streaming on Netflix.

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'Cells At Work!' Will Teach You About Biology, With Gratuitous Violence and an Overload of Cuteness - /FILM

Cell Biology

Organoids, iPSCs, and advanced cell models: Advancing discovery from basic research to drug discovery – Science Magazine

Various in vitro cell culture assays have been used for decades to evaluate disease pathology and uncover potential therapeutic treatments. Despite many successes with these models, they have critical shortcomings. Growing evidence suggests that models providing more predictive and translational observations are desperately needed. Researchers are now moving from reductionist, 2D monoculture assay models to more complex 3D cell models, such as organoids and induced pluripotent stem cell (iPSC) cultures, in order to better evaluate the dynamic interactions between cells in an environment more closely emulating that of the in vivo milieu, and to assess patient-specific phenotypic effects following drug treatment. Effective, well-characterized, advanced cell models hold promise for improving our understanding of disease pathology and progression, and are critical for the identification of novel therapeutic targets.

During this roundtable webinar, the speakers will:

This webinar will last for approximately 60 minutes.

STEMCELL TechnologiesCambridge, UK

Dr. Simmini is an R&D scientist in the gastrointestinal biology group at STEMCELL Technologies. His group focuses on developing products that support the generation of 3D gastrointestinal organoid cultures both from human primary tissue and human induced pluripotent stem cells. Prior to joining STEMCELL Technologies in 2016, he obtained his Ph.D. in stem cells, developmental biology, and cancer at the University of Utrecht in The Netherlands. During that time, he conducted research with the group of Jacqueline Deschamps at the Hubrecht Institute in Utrecht, where he investigated the molecular mechanisms controlled by transcription factor CDX2 in adult mouse intestinal stem cells and during embryonic development. In 2015, he began postdoctoral research, joining the group of Jan Paul Medema and Louis Vermeulen at the Amsterdam Medical Centre in Amsterdam, where he investigated mechanisms regulating intestinal stem cell proliferation and differentiation in colorectal cancer. He is currently involved in several Horizon 2020 European Research Council projects in different roles: researcher within the INTENS (INtestinal Tissue ENgineering Solution) consortium; partner in the SINERGIA (Advanced technologieS for drug dIscovery and precisioN mEdicine: in vitRo modellinG human physiology and diseAse) project; and supervisor and member of the executive board of the Organovir-ETN (Organoids for Virus Research-European Training Network) grant.

Wellcome Sanger InstituteCambridge, UK

As a staff scientist at the Wellcome Sanger Institute, Dr.Hale undertakes basic research projects into hostbacterial interactions while also teaching relevant skills to students and visiting scientists. Her projects include growing and differentiating human induced pluripotent stem cells to either a macrophage-like lineage or as intestinal 3D organoids, then utilizing them to investigate pathogen interactions. The main techniques used are flow cytometry, confocal imaging, high-throughput Cellomics assays, Luminex cytokine assays, and cell culture. The pathogens have varied over the years, but have included Salmonella, Klebsiella, enteropathogenic Escherichia coli (EPEC), Chlamydia, and Leishmania.

UK Dementia Research InstituteCambridge, UK

Dr. Avezov received his Ph.D. in cell research and immunology from the George S. Wise Faculty of Life Sciences at Tel Aviv University in 2010. He conducted his postdoctoral work at the University of Cambridge Wellcome-MRC Institute of Metabolic Science and the Cambridge Institute for Medical Research until 2017 with David Ron, FRS. Quantitative cell biology in the context of human disease has been at the core of Dr. Avezovs research. Working at the interface of biomedical research, physics, and mathematical sciences, he developed the cross-disciplinary expertise for probing intracellular chemical and physical processes in real time. This enabled discoveries of unexpected features of the endoplasmic reticulum (ER), such as an active ER luminal transport mechanism. These findings provide insights into the roles of the ER and its morpho-regulation in neuronal (patho)physiology. Dr. Avezov is currently a UK Dementia Research Institute Group Leader running an interdisciplinary program that seeks to understand early contributions of fundamental cellular processes ranging from ER transport to neurodegeneration.

Science/AAASWashington, D.C.

Dr. Oberst did her undergraduate training at the University of Maryland, College Park, and her Ph.D. in Tumor Biology at Georgetown University, Washington D.C. She combined her interests in science and writing by pursuing an M.A. in Journalism from the Philip Merrill College of Journalism at the University of Maryland, College Park. Dr. Oberst joined Science/AAAS in 2016 as the Assistant Editor for Custom Publishing. Before then she worked at Nature magazine, the Howard Hughes Medical Institute, The Endocrine Society, and the National Institutes of Mental Health.

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Organoids, iPSCs, and advanced cell models: Advancing discovery from basic research to drug discovery - Science Magazine

Cell Biology

How do cells regulate proteins that are on the outside of their membranes? – Medical News Bulletin

Scientists investigate how cells regulatethe proteins that are on the outside of their membranes. This research couldprovide important clues to help develop treatments for Alzheimers disease.

Proteins are the complex molecules that play a critical role in cell biology. They are made up of a chain of amino acids that fold up to form a 3D structure and shape. Each protein has a unique structure that determines its function. Think of proteins like tools, hammers and screwdrivers have different shapes but they are each designed to perform a very specific task. Proteins are made in the cell and sometimes they dont fold correctly or their structural integrity is damaged due to stresses like high temperatures and oxidative stress. This can be dangerous as the abnormal proteins can aggregate and cause damage in the cell. This can lead to a range of illnesses called protein deposition diseases such as Alzheimers disease, Huntingtons disease, and Parkinsons disease. In the case of Alzheimers disease, beta-amyloid peptides are toxic because they stick together and form aggregates. These are often secreted outside the cell and the aggregates then stick to extracellular molecules and form plaques.

Protein quality control systems

In healthy cells, there are protein quality control systems in place to make sure proteins fold correctly. One of these systems uses chaperones, these are proteins whose sole job is to ensure that other proteins are the correct shape. If the target proteins are incorrectly folded one of two things happens, either the chaperone uses energy (in the form of ATP) to refold the protein or the entire protein is degraded.

What happens to the proteins that are secreted and function outside of the cell?

Not all proteins are designed to workwithin the cell. These proteins can be susceptible to damage from stressorssuch as pathological conditions, shear stress, and acidosis and alkalosis (incorrectpH). So what happens when these proteins undergo structural changes? Somechaperone proteins are also secreted, such as clusterin. The problem is thatthere is a thousand times less ATP (energy) outside the cell, meaning that thesechaperones cant refold misfolded proteins. The exact mechanism of how thechaperons work outside the cell is not well understood.

How does clusterin work?

In a recently published article in the Journal of Cell Biology, scientists fromJapan wanted to know how clusterin worked. They speculated that clusterinworked by binding to misfolded proteins and bringing them into contact with thecell. The cell would then engulf the clusterin and misfolded protein complexand degrade it.

New internalisation test developed

The first question the researchers askedwas if clusterin that is bound to a misfolded protein would be able to getinside the cell. They wanted to know if these proteins would be broken downinside a cell structure called the lysosome. Lysosomes are another proteinquality control system and they are responsible for degrading proteins with anacidic environment and digestive enzymes.

The scientists designed a newinternalisation test to help them answer these questions. They used geneticengineering to attach two fluorescent proteins to clusterin (one green and theother red). The red fluorescent protein is resistant to acidic conditions anddigestive enzymes. So if the scientists saw red under the microscope they couldconclude clusterin was indeed internalised and degraded but if they saw onlygreen they could conclude that the clusterin was internalised but not degraded.The scientists combine their internalisation assay with flow cytometry andfluorescent microscopy to show that the Clusterin-misfolded protein complex waspreferentially internalised and degraded with a lysosome. The team used variouscell types (kidney, ovary, lung, bone, liver, and colon) to test their assayand showed this internalisation occurred generally. They then went to show thatthe beta-amyloid peptide was able to bind to clusterin and was subsequentlydegraded in human embryonic kidney cells.

What is the clusterin receptor?

The scientists wanted to know if there wasa receptor on the cell surface that bound to clusterin and triggered theinternalisation of this complex. The team used a genome-wide CRISPR screen tofind out which genes were important for clusterin uptake. They identified 20different genes important for uptake of clusterin and many of them wereimplicated in heparan sulphate (HS) synthesis. To test if HS was the receptorfor clusterin the scientists used genetic engineering to prevent the expressionof various genes involved in the HS pathway. They found that when these geneswere knocked out there was reduced uptake of the clusterin-misfolded proteincomplex. When they restored the gene expression they found this restoredcomplex uptake. This data showed that HS pathway disruption preventedinternalisation of only the clusterin complex and not of endocytosis ingeneral. The scientists then used a pull-down assay to confirm that clusterindirectly binds to HS. These data strongly suggested that HS is the receptor forthe uptake of clusterin-misfolded protein complexes. The group went on to show that HS was theclusterin receptor independent of the misfolded proteins bound. They testedbeta-amyloid peptide and a variety of misfolded red blood cell proteins.

The researchers were able to show anentirely novel mechanism for regulating extracellular proteins called thechaperone- and receptor-mediated extracellular protein degradation (CRED)pathway. Although this is an exciting discovery the involvement of the pathwayin Alzheimers disease requires further investigation. The tests onbeta-amyloid peptides were conducted in kidney cells and not neuronal celllines. There was also no investigation into whether or not this mechanism worksin animals. It seems unlikely that increasing clusterin expression will resultin a treatment for Alzheimers disease as overexpression of this protein hasbeen linked to cancer pathogenesis. The work present is an excitingcontribution to our basic understanding of protein regulation outside the celland is promising progress toward understanding many of the protein depositiondiseases.

Written by Tarryn Bourhill MSc, PhD Candidate.

References:

1 Yerbury, J. J., Stewart, E. M.,Wyatt, A. R. & Wilson, M. R. Quality control of protein folding inextracellular space. EMBO reports 6, 1131-1136 (2005).

2 Jones, S. E.& Jomary, C. Clusterin. Theinternational journal of biochemistry & cell biology 34, 427-431 (2002).

3 Nuutinen, T.,Suuronen, T., Kauppinen, A. & Salminen, A. Clusterin: a forgotten player inAlzheimers disease. Brain researchreviews 61, 89-104 (2009).

4 Wyatt, A. R.,Yerbury, J. J., Ecroyd, H. & Wilson, M. R. Extracellular chaperones andproteostasis. Annual review ofbiochemistry 82, 295-322 (2013).

5 Itakura, E., Chiba, M., Murata, T. & Matsuura, A. Heparan sulfate is a clearance receptor for aberrant extracellular proteins. Journal of Cell Biology 219 (2020).

Image byKonstantin KolosovfromPixabay

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