How Does SARS-CoV-2 Invade Our Bodies So Easily? / In che modo SARS-CoV-2 invade i nostri corpi così facilmente?
How Does SARS-CoV-2 Invade Our Bodies So Easily? / In che modo SARS-CoV-2 invade i nostri corpi così facilmente?
Segnalato dal Dott. Giuseppe Cotellessa / Reported by Dr. Giuseppe Cotellessa
In order for a COVID-19 vaccine and antiviral drugs to be developed, scientists first need to understand why this virus spreads so easily and quickly, and why it invades our bodies with seemingly little resistance from our immune system.
To understand how COVID-19 enters the body and does its damage, a team of top researchers from universities, hospitals and the National Research Council of Canada (NRC) at the Centre for Research and Application in Fluidic Technologies, or CRAFT (a collaborative centre between the University of Toronto and the NRC), are adapting an approach developed by U of T’s Milica Radisic, Axel Guenther and Edmond Young to create miniscule models of the nose, mouth, eyes and lungs.
The focus will be on understanding why this virus is so effective at breaking through the body’s natural defenders against viral and bacterial invaders, otherwise known as epithelial barriers. These barriers – created by epithelial cells that pack themselves tightly together – are present throughout our bodies.
“Normally, these epithelial barriers do a good job of helping us fight infections,” says Radisic, who is a professor in the department of chemical engineering and applied chemistry in the Faculty of Applied Science & Engineering.
“But this virus has found a way to invade the barriers. That’s our focus – why is this?”
In recent years, Radisic’s research has allowed her to make important progress in developing models of the heart on computer chips. The hearts – made from human cells – capture the key functions of an actual heart. That research, in turn, has been extremely effective in regenerating heart cells. Radisic has also used this organ-on-a-chip model to study how nanoparticles from air pollution damage our organs.
Now, by creating mini-models of other human organs,the researchers can take a detailed view of just how COVID-19 is working.
“This method allows us to study the problem without having to touch a human and potentially harm someone,” says Radisic, who is also Canada Research Chair in Functional Cardiovascular Tissue Engineering.
“That’s the beauty of it. We can do our research early in the viral infection. You can’t do that with a human, because once you know you have COVID-19, you’ve been infected for two weeks. With organ-on-a-chip, we can study what happens within 24 hours of COVID-19 entering the body.”
A big part of the challenge with COVID-19 is that it’s new and no one is immune.
“There isn’t anyone who has developed the T and B cells that are part of what we call ‘adaptive immunity’ – the cells you build up as you are exposed to diseases. We are all born with innate immunity. This works early when we are invaded with a virus. It finds things that don’t belong in your body and tries to clean it up.”
Radisic says having a lung-on-a-chip will enable the team to study the innate early response of the immune system to COVID-19.
Once the models are built with commercially available cell lines to set the groundwork, the human cells for the organs-on-a-chip will be supplied by CRAFT members Tereza Martinu (respirology) and Ana Konvalinka (nephrology) of University Health Network and U of T’s Faculty of Medicine. The live virus will be acquired from Karen Mossman, a researcher in pathology and molecular medicine at McMaster University. Mossman was involved in isolating the virus with U of T scientists Samira Mubareka and Robert Kozak, who are based at Sunnybrook Health Sciences Centre.
“Karen has the live virus, so we will give her the chips and she will infect the organs in a special level three facility,” Radisic says.
Other CRAFT team researchers include Teodor Veres and his colleagues Daniel Brassard, Lidija Malic and Sue Twine from the NRC; Guenther and Young, both of U of T’s Faculty of Applied Science & Engineering; and Wolfgang Kuebler of the Keenan Research Centre for Biomedical Science, St. Michael’s Hospital and surgery and physiology at U of T.
The group will also experiment with the “Powerblade,” a technology the NRC in Montreal is using to test the blood of astronauts while on space missions. It will be repurposed by the research team to examine its potential for testing people with COVID-19 when they arrive at a hospital.
“Once we figure out which molecules are biomarkers for a severe case of COVID-19, the Powerblade will be able to read that at point-of-care,” Radisic says.
“The health-care providers will then know how your innate immunity is reacting and if the virus will be severe or not. The problem with COVID-19 is that it works fast. You look good one minute and then, suddenly, you can be in real trouble. So getting earlier markers is important.”
To understand how COVID-19 enters the body and does its damage, a team of top researchers from universities, hospitals and the National Research Council of Canada (NRC) at the Centre for Research and Application in Fluidic Technologies, or CRAFT (a collaborative centre between the University of Toronto and the NRC), are adapting an approach developed by U of T’s Milica Radisic, Axel Guenther and Edmond Young to create miniscule models of the nose, mouth, eyes and lungs.
The focus will be on understanding why this virus is so effective at breaking through the body’s natural defenders against viral and bacterial invaders, otherwise known as epithelial barriers. These barriers – created by epithelial cells that pack themselves tightly together – are present throughout our bodies.
“Normally, these epithelial barriers do a good job of helping us fight infections,” says Radisic, who is a professor in the department of chemical engineering and applied chemistry in the Faculty of Applied Science & Engineering.
“But this virus has found a way to invade the barriers. That’s our focus – why is this?”
In recent years, Radisic’s research has allowed her to make important progress in developing models of the heart on computer chips. The hearts – made from human cells – capture the key functions of an actual heart. That research, in turn, has been extremely effective in regenerating heart cells. Radisic has also used this organ-on-a-chip model to study how nanoparticles from air pollution damage our organs.
Now, by creating mini-models of other human organs,the researchers can take a detailed view of just how COVID-19 is working.
“This method allows us to study the problem without having to touch a human and potentially harm someone,” says Radisic, who is also Canada Research Chair in Functional Cardiovascular Tissue Engineering.
“That’s the beauty of it. We can do our research early in the viral infection. You can’t do that with a human, because once you know you have COVID-19, you’ve been infected for two weeks. With organ-on-a-chip, we can study what happens within 24 hours of COVID-19 entering the body.”
A big part of the challenge with COVID-19 is that it’s new and no one is immune.
“There isn’t anyone who has developed the T and B cells that are part of what we call ‘adaptive immunity’ – the cells you build up as you are exposed to diseases. We are all born with innate immunity. This works early when we are invaded with a virus. It finds things that don’t belong in your body and tries to clean it up.”
Radisic says having a lung-on-a-chip will enable the team to study the innate early response of the immune system to COVID-19.
Once the models are built with commercially available cell lines to set the groundwork, the human cells for the organs-on-a-chip will be supplied by CRAFT members Tereza Martinu (respirology) and Ana Konvalinka (nephrology) of University Health Network and U of T’s Faculty of Medicine. The live virus will be acquired from Karen Mossman, a researcher in pathology and molecular medicine at McMaster University. Mossman was involved in isolating the virus with U of T scientists Samira Mubareka and Robert Kozak, who are based at Sunnybrook Health Sciences Centre.
“Karen has the live virus, so we will give her the chips and she will infect the organs in a special level three facility,” Radisic says.
Other CRAFT team researchers include Teodor Veres and his colleagues Daniel Brassard, Lidija Malic and Sue Twine from the NRC; Guenther and Young, both of U of T’s Faculty of Applied Science & Engineering; and Wolfgang Kuebler of the Keenan Research Centre for Biomedical Science, St. Michael’s Hospital and surgery and physiology at U of T.
The group will also experiment with the “Powerblade,” a technology the NRC in Montreal is using to test the blood of astronauts while on space missions. It will be repurposed by the research team to examine its potential for testing people with COVID-19 when they arrive at a hospital.
“Once we figure out which molecules are biomarkers for a severe case of COVID-19, the Powerblade will be able to read that at point-of-care,” Radisic says.
“The health-care providers will then know how your innate immunity is reacting and if the virus will be severe or not. The problem with COVID-19 is that it works fast. You look good one minute and then, suddenly, you can be in real trouble. So getting earlier markers is important.”
ITALIANO
Affinché sia sviluppato un vaccino COVID-19 e farmaci antivirali, gli scienziati devono prima capire perché questo virus si diffonde così facilmente e rapidamente e perché invade i nostri corpi con apparentemente poca resistenza dal nostro sistema immunitario.
Per capire come COVID-19 entra nel corpo e fa il suo danno, un gruppo di ricercatori di spicco di università, ospedali e del National Research Council of Canada (NRC) presso il Center for Research and Application in Fluidic Technologies, o CRAFT (un centro collaborativo tra l'Università di Toronto e la NRC), stanno adattando un approccio sviluppato da Milica Radisic di U of T, Axel Guenther e Edmond Young per creare minuscoli modelli di naso, bocca, occhi e polmoni.
L'attenzione sarà focalizzata sulla comprensione del perché questo virus è così efficace nel rompere i naturali difensori del corpo contro gli invasori virali e batterici, altrimenti noti come barriere epiteliali. Queste barriere - create da cellule epiteliali che si uniscono strettamente insieme - sono presenti in tutti i nostri corpi.
"Normalmente, queste barriere epiteliali fanno un buon lavoro nell'aiutarci a combattere le infezioni", afferma Radisic, che è professore nel dipartimento di ingegneria chimica e chimica applicata presso la Facoltà di Scienze Applicate e Ingegneria.
“Ma questo virus ha trovato il modo di invadere le barriere. Questo è il nostro obiettivo: perché? "
Negli ultimi anni, la ricerca di Radisic le ha permesso di compiere importanti progressi nello sviluppo di modelli del cuore su chip per computer. I cuori - fatti da cellule umane - catturano le funzioni chiave di un cuore reale. Quella ricerca, a sua volta, è stata estremamente efficace nel rigenerare le cellule cardiache. Radisic ha anche usato questo modello organo su chip per studiare come le nanoparticelle dall'inquinamento atmosferico danneggiano i nostri organi.
Ora, creando mini-modelli di altri organi umani, i ricercatori possono avere una visione dettagliata di come funziona COVID-19.
"Questo metodo ci consente di studiare il problema senza dover toccare un essere umano e potenzialmente danneggiare qualcuno", afferma Radisic, che è anche presidente della ricerca canadese in ingegneria funzionale del tessuto cardiovascolare.
"Questa è la bellezza. Possiamo fare le nostre ricerche all'inizio dell'infezione virale. Non puoi farlo con un essere umano, perché una volta che sai di avere COVID-19, sei stato infettato per due settimane. Con l'organo-su-un-chip, possiamo studiare cosa succede entro 24 ore dall'ingresso di COVID-19 nel corpo. "
Una grande parte della sfida con COVID-19 è che è nuova e nessuno è immune.
"Non c'è nessuno che abbia sviluppato le cellule T e B che fanno parte di quella che chiamiamo" immunità adattativa ": le cellule che accumuli quando sei esposto a malattie. Siamo tutti nati con immunità innata. Funziona presto quando siamo invasi da un virus. Trova cose che non appartengono al tuo corpo e cerca di ripulirlo. "
Radisic afferma che avere un polmone su un chip consentirà al gruppo di studiare l'innata risposta precoce del sistema immunitario a COVID-19.
Una volta costruiti i modelli con linee cellulari disponibili in commercio per impostare le basi, le cellule umane per gli organi su un chip saranno fornite dai membri del CRAFT Tereza Martinu (respirologia) e Ana Konvalinka (nefrologia) di University Health Network e U della facoltà di medicina di T. Il virus vivo sarà acquisito da Karen Mossman, ricercatrice in patologia e medicina molecolare presso la McMaster University. Mossman è stato coinvolto nell'isolamento del virus con gli scienziati di U of T Samira Mubareka e Robert Kozak, che hanno sede presso il Sunnybrook Health Sciences Center.
"Karen ha il virus vivo, quindi le daremo i modelli e infetterà gli organi in una struttura di livello tre speciale", afferma Radisic.
Altri ricercatori del team CRAFT includono Teodor Veres e i suoi colleghi Daniel Brassard, Lidija Malic e Sue Twine del NRC; Guenther e Young, entrambi della facoltà di scienze e ingegneria applicata di U; e Wolfgang Kuebler del Keenan Research Center for Biomedical Science, St. Michael's Hospital e chirurgia e fisiologia presso la U di T.
Il gruppo sperimenterà anche il "Powerblade", una tecnologia che la NRC di Montreal sta usando per testare il sangue degli astronauti durante le missioni spaziali. Sarà riproposto dal gruppo di ricerca per esaminare il suo potenziale per testare le persone con COVID-19 quando arrivano in ospedale.
"Una volta scoperto quali molecole sono biomarcatori per un caso grave di COVID-19, Powerblade sarà in grado di leggerlo nel punto di cura", afferma Radisic.
“I fornitori di assistenza sanitaria sapranno quindi come reagisce la tua immunità innata e se il virus sarà grave o meno. Il problema con COVID-19 è che funziona velocemente. Stai bene un minuto e poi, all'improvviso, potresti essere nei guai. Quindi è importante ottenere marcatori precedenti. "
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