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  • 00:04

    SIMON PAMPENA: Can you imagine beingfaced with a jigsaw of 3.6 million pieces?Where do you start?But if by completing the puzzle you could help eradicate someof the most debilitating viruses the world's ever knownand, with the help of a supercomputer,you might be motivated to tackle the problem.

  • 00:26

    SIMON PAMPENA [continued]: Medical scientists Jason Roberts and Bruce Thorleyhave constructed the first simulated modelof the polio virus.ASSOC.PROF.

  • 00:32

    BRUCE THORLEY: The beauty of these modelsis that they are actually a simulation,they're not an animation.It's a simulation of the viral structureusing biophysical computations.[ASSOC.PROF.BRUCE THORLEY, POLIOVIRUS REFERENCE LABORATORY VIDRL]

  • 00:42

    JASON ROBERTS: In the 50s, during the massive Polioepidemics, a model like this wouldhave been extremely useful to just geta general understanding of the mechanisms of the virus.What is-- know your enemy.What are we dealing with?[JASON ROBERTS, SENIOR MEDICAL SCIENTIST VIDRL]

  • 00:56

    SIMON PAMPENA: The polio reference laboratoryin Melbourne is one of a network of labsworking with the World Health Organizationto eradicate polio.

  • 01:04

    SPEAKER 1: Yes, that just arrived.ASSOC.PROF.

  • 01:08

    BRUCE THORLEY: In the 1900s we startedto see polio epidemics worldwide,and early on it was mainly children who were infected.Unfortunately, there's no cure for polio.

  • 01:19

    SIMON PAMPENA: But since the introductionof the global eradication program in 1998,2.5 billion children have been immunized.Reported cases of wild polio havedropped from 350,000 in 1988 to just over 200 in 2012.ASSOC.PROF.

  • 01:37

    BRUCE THORLEY: Three countries remain endemicfor wild polio virus, Afghanistan, Nigeria,and Pakistan.

  • 01:43

    SIMON PAMPENA: Because of its placein human history and the devastation it has caused,the polio virus has been extremely well studied.But up until now, research has onlybeen based on static images of the virus.

  • 01:57

    JASON ROBERTS: There's no technology available thatcan allow you to look at the individual atomic movementsand interactions in real time.You can take snapshots using microscopy techniques,or you can use x-ray diffraction and crystallographymethods which are really, really complicated.There's not a lot of options available to actually studyan individual virus particle and how it behaves.

  • 02:20

    SIMON PAMPENA: But Jason uses these images as templatesto construct his virus models.

  • 02:26

    JASON ROBERTS: So this single componentis one of 60 components that are required to make upthe full virus shell.And we took the genetic informationand we folded that up and actually placedthat inside the virus as well.You can see the genetic information in the core, here.And this is the caps on the outside.Initially it's a snapshot, but when

  • 02:46

    JASON ROBERTS [continued]: you combine it with a supercomputer,it becomes a simulation.

  • 02:52

    SIMON PAMPENA: So how critical was this supercomputerin doing your calculations?

  • 02:56

    JASON ROBERTS: Completely vital.We wouldn't be able to do the work at all.We're talking billions and billions of calculationsevery second, and a desktop computeris just not capable of doing that sort of work.

  • 03:08

    SIMON PAMPENA: The simulated modelallows Jason to study the mechanicsof a virus at an atomic level to testit's behavior in different environmentsand to see how it reacts to drugs.

  • 03:23

    JASON ROBERTS: The drugs are now basically attacking the virus.We are interested in this blue areahere, where we can see our drug wobbling around.The advantage of having our 60 pieces that are identicalis that we then have 60 different places wherewe can bind the drug.

  • 03:38

    SIMON PAMPENA: And in effect, that's 60 experiments allhappening at once.

  • 03:42

    JASON ROBERTS: We can develop our methodsto come up with a way to say yes, this virus is resistant,or yes, this virus is sensitive to this drug.And then if the virus was to become an epidemic,then we might be able to predict which drug would be useful.

  • 03:56

    SIMON PAMPENA: And quite by accident, the simulationalso revealed how a viral infection may occur.

  • 04:02

    JASON ROBERTS: I noticed that the RNA,or the genetic information, had actuallystarted to squeeze out of a particular split in the virus.And it was around the same time that a group at HarvardUniversity had published an in vitro observation showingthat the RNA came out at a particular point in the virusunder heating.And when I went back to my model,I noticed that my model fitted exactly what they observed.

  • 04:25

    SIMON PAMPENA: Wow.Based on this and other research,Jason has been able to validate his work.

  • 04:31

    JASON ROBERTS: We observed this behavior in the simulations.How does that reflect what's beenshown in the actual manuscripts and what'sbeen published in the scientific community?And so far it has been accurate.

  • 04:44

    SIMON PAMPENA: With such encouraging results,Jason's now modeling other viruses.

  • 04:49

    JASON ROBERTS: You're talking about common cold, diarrhea,deadly brain infections.A lot of these viruses follow the same sortof construction kit.

  • 05:01

    SIMON PAMPENA: And that's good news,given Jason has recently discovered a new virus,classified as enterovirus A120.

  • 05:10

    JASON ROBERTS: We've actually developed a series of detectionmethods that we were trialing, and westumbled across an enterovirus from a paralyzed child.When we were able to get some sequence outof it, which took a number of years of trying,we tested that and found that it was actuallya completely new virus that had never been seen before.

  • 05:31

    JASON ROBERTS [continued]: We're able to use the toolkit to build the virus shell,and I did that in an hour.

  • 05:40

    SIMON PAMPENA: And this begs the question,could these model simulations do away with clinical trials?

  • 05:46

    JASON ROBERTS: Absolutely not.Every human is different and theywill respond differently to different viruses,to different drugs.So clinical trials are absolutely essential.

  • 05:55

    SIMON PAMPENA: What's the payoff?

  • 05:56

    JASON ROBERTS: The payoff for these models I would hopewould be to provide a generalized toolkit, that wehave a series of models, pharmaceutical companiesor researchers can take the model so they can thengo and put their drug inside the virus, run a simulation,and actually look at the atomic level, what's the mechanism?What's actually going on here?How is this virus interacting with the drug?

  • 06:18

    JASON ROBERTS [continued]: And does that fit with my hypothesis?ASSOC.PROF.

  • 06:21

    BRUCE THORLEY: I believe the development of the modelsthat Jason has produced does have the potentialto help with rational drug design,and so that would speed up the production of anti-virals.

  • 06:33

    SIMON PAMPENA: Bio research in a virtual worldis critical, because like smallpox,once polio and other significant viruses are finally eradicated,there will only be a few select labs worldwide thatwill hold these live viruses.

  • 06:49

    JASON ROBERTS: If you are examining a virus that'sknown to be a killer virus, you don'tneed to manipulate that virus in a high security containmentlaboratory.You can take just the genetic information,you could email it to yourself or someonecould email it to you and say, we have this dangerous virus.You can reconstruct the virus and youcan do the work in silico.

  • 07:10

    JASON ROBERTS [continued]: You could be sitting at a desk in an office.

  • 07:12

    SIMON PAMPENA: With minds and technology like this,the eradication of polio and other significant virusesappears within our reach.

Video Info

Publisher: Australian Broadcasting Company

Publication Year: 2013

Video Type:Documentary

Methods: Simulation, Computational modelling, Data visualization

Keywords: clinical trials; computer models; computer simulations; drug treatment; enterovirus infections; epidemics; immunization programs; immunization/vaccination; polio; RNA viruses; Simulation modeling; Smallpox; vaccines; viral infections; viruses ... Show More

Segment Info

Segment Num.: 1

Persons Discussed:

Events Discussed:

Keywords:

Abstract

Simon Pampena outlines current advances in computer-based virus simulations, focusing on Jason Robert's work with the polio virus. The virus simulation provides insights on how viral infections can occur and behave, and serves as a model toolkit for further research on other viruses.

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3D Virus

Simon Pampena outlines current advances in computer-based virus simulations, focusing on Jason Robert's work with the polio virus. The virus simulation provides insights on how viral infections can occur and behave, and serves as a model toolkit for further research on other viruses.

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