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the international space station is a

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state-of-the-art research laboratory

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that allows scientific research to be

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performed in the microgravity of space

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research in this unique microgravity

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environment is advancing our knowledge

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of biology chemistry physics and

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physiology

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scientists from all over the world are

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using facilities on this high-flying

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international laboratory that is packed

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with some of the most sophisticated

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technologies ever designed

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space station research brings new

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discoveries furthers technology

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development expands our limits of

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exploration

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hi i'm mark gott i work here at the

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johnson space center in the microbiology

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lab our job in the microbiology lab is

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to protect the crew from possible

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problems that could occur due to

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microorganisms so we take a look at the

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environment the crew themselves and the

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food they eat just to make sure that

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they're safe during a mission

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we know a lot about what goes on in

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space flight with the international

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space station we've learned a tremendous

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amount about how the crew responds what

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it takes to keep them healthy and what

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kind of problems you have in the

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environment that may occur over time

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however we haven't always known a lot

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and we still have a lot of questions to

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ask that's why we do a lot of research

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one of the challenges we face with

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astronauts in space flight is that we

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found with some of our research that

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their immune system is regulated in a

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different way and we're worried it could

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be dysfunctional

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what does this mean

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it's possible that the crew could be

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more susceptible to infectious disease

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good morning my name is dr cheryl

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nickerson i'm a professor in the center

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for infectious diseases and vaccinology

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at the biodesign institute at arizona

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state university

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so research in my laboratory here is

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focused on two main things first of all

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we're interested in understanding how

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space flight alters the infectious

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disease risk because we want to keep the

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crew the astronauts safe and mitigate

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their risk for infection when they're

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flying but likewise it turns out through

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the studies we've done in my laboratory

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and with dr ott we have been able to

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show that there are aspects of that

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microgravity environment that cells

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encounter when they're cultured in space

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flight that are directly relevant to

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what those same microbial pathogens

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encounter when they're in your body

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during an infection well it all got

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started several years ago when mark ott

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at the nasa johnson space center called

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me up on the phone and said that the

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astronauts were aiming to compromise

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during space flight now that means their

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immune system doesn't function quite as

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well as it does when they're down here

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on earth on a daily basis and this

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intrigued me because my background in

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career training was in microbial

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pathogenesis in other words i study how

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microbes cause disease the cellular and

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molecular mechanisms that they use to

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cause disease in your body by studying

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those mechanisms we can then apply that

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knowledge to develop new vaccines and

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therapeutics and treatments to prevent

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you from getting sick from infection

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so i realized we knew half of the

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equation we knew that spaceflight

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altered the immune system but we didn't

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know the other half of the equation and

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the other half of the equation is also

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very important to determine whether or

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not you're going to get sick after you

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get infected and that has to do with the

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virulence of the pathogen of virulence

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means disease-causing potential but

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nobody had looked at the effect of space

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flight on the disease-causing potential

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so i immediately asked dr ott what i

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thought at the time might be a very

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silly question and this should always

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teach you always ask questions no

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question is ever silly no question is

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ever done so i asked him i said well

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this is amazing i said

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we have to look at the effect of space

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flight on the infectious disease

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potential the pathogen has anybody ever

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done that and his response was no they

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haven't so i immediately followed that

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question was well we have to do this can

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we fly an experiment now

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that was my naivete because i didn't

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realize you had to go through a very

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long series of ground-based studies to

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validate that you really needed to use

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the space flight experiment to to

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address your potential question i said

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okay until we can fly is there some way

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that we can mimic some system that we

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can use to mimic to culture these

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bacterial cells here in the laboratory

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on earth under conditions which mimic

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space flight so this is that special

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bioreactor that nasa design that allows

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scientists like me to culture ourselves

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in the laboratory under conditions which

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both simulate aspects of the

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microgravity environment and stimulate

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aspects of inside our human bodies

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so we have been able to use this

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bioreactor to grow pathogens under

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conditions in ways that they actually

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experience in your body in addition to

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similar ways in space light and find new

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ways that they're causing disease in the

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body for example my laboratory in

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collaboration with dr oz laboratory has

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shown that when we culture pathogens in

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this bioreactor especially salmonella a

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major human foodborne pathogen it causes

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disease not only differently but it

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globally changes its gene expression

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profile

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it becomes a better pathogen it can

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cause disease more effectively it's more

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robust pathogen and it can also be more

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resistant to being killed by stresses

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that your body normally challenges it

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with so armed with this information this

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new insight we've been able to provide

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about how salmonella could cause disease

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in the body by culturing it under space

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flight like conditions we were awarded a

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grant from nasa our first one to fly a

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space flight experiment

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so this is the experiment we were funded

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in a grant with nasa to fly what is the

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effect of true space flight on

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salmonella gene expression and

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disease-causing potential or virulence

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now one thing to keep in mind is that

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space flight doing experiments in space

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flight is very different than doing them

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here on the bench on earth you have to

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think differently and there's a whole

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lot of constraints that you're going to

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have to consider

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one of them to think about is we wanted

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to study the effect of space flight on

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the infectious disease potential of a

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pathogen

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well

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the problem is

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nasa at the time did not allow anything

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to be infected in flight so you could

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only grow the bacteria up there and

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activate them and prepare them for the

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experiment but the actual infections

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have to be done back down here so

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something to keep in mind when you're

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when you're designing your experiment

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now that you've heard the background

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from dr cheryl nickerson about this

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project

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i'd like you to try to set up the

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experiment

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and what would your hypothesis be

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i'd like you to design an experiment

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that will investigate the effect of

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space flight on the genetic responses

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and disease-causing potential or

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virulence of salmonella typhomerium

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when designing this experiment

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don't forget

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proper containment of the experiment

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needs to be maintained to pose no threat

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to crude during or after spaceflight

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the experiment must be activated in the

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in space flight and coordinated with

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activation of ground-based controls

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strict timelines must be designed into

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your experiment to coordinate with the

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experimental return to the investigator

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post-flight must be rapid to ensure

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sample integrity for analysis on earth

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and as with all spaceflight experiments

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try to use very little crew time and

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minimize the hardware volume

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so the hypothesis of this experiment is

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that space flight will affect gene

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expression and virulence of

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salmonella-type femorium you were given

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a series of constraints that you had to

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give careful consideration to in

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designing your experiment proper

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containment of the experiment to pose no

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threat to the crew during space flight

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our hardware or the containers that we

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used to fly this experiment that would

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actually activate the work in space had

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to have what we call triple levels of

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containment so that there were three

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barriers between the crew who are

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performing the experiment and them ever

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having any risk of it coming into

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contact with it the experiment has to be

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activated in space flight and

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coordinated with activation of

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ground-based controls my entire team was

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at the kennedy space flight center and

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that's where we prepared the experiment

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and we prepared two duplicate sets of it

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we had two identical sets of our flight

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hardware and we loaded them at the same

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exact time with all reagents including

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our strain of salmonella

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the fixative reagents which would be for

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gene expression and then the growth

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medium and everybody was loaded at the

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same time and half of that hardware flew

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and the other half stayed on the ground

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for the timing to activate the

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experiment

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we were linked in real time with

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astronauts so when the astronauts were

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activating our experiment on orbit they

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called down to us we were in that room

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at the same time and we activated and

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did everything to our controls in that

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special room at the same time that they

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did on orbit strict timelines must be

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designed in your experiment to

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coordinate with the astronaut schedules

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so you have to design a space flight

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experiment and your biological system

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has to be adaptable and and your

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experiment

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can't fail if it's performed a little

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bit outside of the timeline of what

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would be ideal so you have to tell the

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crew i want my experiment to be

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activated at this time but i can take

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this much time ahead or behind it so

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plus or minus a certain number of hours

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or minutes that you can allow for your

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experiment the experiment is returned to

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the investigator post-flight it has to

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be returned to us very rapidly to ensure

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two things sample integrity for earth

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and also that the bacteria are are not

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re-adapting to being back in earth's

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gravity because we were testing two

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things remember our hypothesis is that

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space flight affects gene expression and

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expects severe it affects virulence so

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two things happen to our samples on

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orbit and obviously on the ground as

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well half of the samples after the

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bacteria were activated for growth they

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grew to a certain period of time and

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then the astronauts terminated that half

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of the experiment they fixed it with a

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chemical to preserve the the uh the

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experiment for gene expression analysis

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the other half of the bacteria for

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virulence that half of the bacterium

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after they were growing they were

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brought back live so as soon as the

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shuttle landed we had a special

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requirement for what we call first off

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which means that after the crew comes

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off the shuttle our experiment is

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unloaded immediately

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and then we had to try to use very

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little crew time so

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astronaut time is incredibly valuable

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and you don't get very much of it so you

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either have to work with hardware that's

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fully automated or you have to design

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your experiment so that the crew has

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minimal amount of time that they have to

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invest in doing your experiment although

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i will say the crew is awesome the

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astronauts always want to give extra

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time to do science your experiment has

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to be designed to minimize hardware

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volume minimize mass and power needs you

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need to really minimize the amount of

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volume that you're sending up in flight

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and that can pose a challenge for your

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downstream analysis of your samples

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because you have to have enough volume

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to get enough sample to be analyzed for

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both gene expression and virulence

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you obviously have to minimize mass

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because size constraints matter you want

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to fly

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as small of volumes as possible and

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power needs because most of the power

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has to go to run the shuttle

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so we were very fortunate that our

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experiments could fly just at ambient or

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room temperature and the bacterial cells

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would be fine and we actually had the

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astronauts performing manually our

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experiments for us so we didn't need the

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hardware to be

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as much of a power drain to the shuttle

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so what did we find from our spaceflight

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experiment with salmonella well we found

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that spaceflight uniquely increased the

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virulence of this pathogen and it also

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globally changed its gene expression

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profile and the unique part of the

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change in gene expression profile is

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that the genes that were being turned on

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and off weren't being turned on and off

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in a manner that would be consistent

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with salmonella actually being more

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virulent actually being able to cause

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disease better so what this taught us is

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that salmonella is causing disease in a

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different manner than we can detect when

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we grow it conventionally on ground when

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we fly at microgravity so greatly

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removing the force of gravity unveiled

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new ways that salmonella is causing

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so i'm one of those people who knew from

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day one i was going to be in biology and

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life sciences i knew it would be in

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biomedical research i just didn't know

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what end of it so my entire career

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training kind of guided me toward that

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trajectory so my undergraduate degree

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was in biology my master's genetics phd

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in microbiology postdoc in bacterial

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pathogenesis and that's where it really

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hit me the infectious disease world is

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where i was going to go i had no idea in

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a million years that i would get the

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privilege and opportunity to work with

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nasa and do space flight research as a

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way to help provide new solutions to

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outpace infectious diseases but i was

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very fortunate to have gone to graduate

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school with mark ott he went to nasa i

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took my first lab position in infectious

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diseases and vaccinology in my first

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faculty position and it's just taken off

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from there the most important thing you

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have to have is passion you find what

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you're passionate about you love it and

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you live it and you contribute in that

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manner to society

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in taking a look at a career path to

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make it to nasa there are a wide variety

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of options

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to get into something like microbiology

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and microbiology research a background

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in microbiology is important there are a

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lot of other majors that can do great

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contributions here degrees in

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biochemistry

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immunology

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looking at general biology

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engineering

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all have a way of joining in when we

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look at the space flight industry

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but remember first and foremost do what

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i did