ON DEAFNESS AND OTHER
COMMUNICATION DISORDERS HERE AT
THE NATIONAL INSTITUTES OF
HEALTH.
ON BEHALF OF THE NIDCD CORRECT
DORDR. DEBORAH TUSSI, WE WOULD
LIKE TO WELCOME YOU TO NIDCD'S
BEYOND THE LAB, UNDERSTANDING
COMMUNICATION DISORDER SPEAKER
SERIES.
AND TODAY'S TALK ZEBRAFISH CAN
HELP US SEE HOW HEARING WORKS,
DR. KATIE KINDT, A SENIOR
INVESTIGATOR HERE AT NIDCD WILL
HELP EXPLAIN HOW HER LAB USES
MOLECULAR AND MICROSCOPY BASED
METHODS TO EXAMINE SENSORY CELL
FUNCTION AND DEVELOPMENT IN THE
ZEBRAFISH MODEL SYSTEM.
ZEBRAFISH ARE USE AS A MODEL FOR
STUDYING HAIR CELLS, THE SENSORY
CELLS OF THE HEARING AND BALANCE
SYSTEMS BECAUSE ZEBRAFISH ARE
FULLY TRANSPARENT AS THEY
DEVELOP.
THIS ALLOWS RESEARCHERS TO SEE
HOW THEIR CELLS DEVELOP AND
FUNCTION AS A ZEBRAFISH MATURES.
BY UNDERSTANDING HOW HAIR CELLS
WORK, SCIENTIST CANS DEVELOP NEW
TREATMENTS AND CURE FOR HEARING
AND BALANCE CONDITIONS.
NIDCD'S MISSION IS TO SUPPORT
RESEARCH AND RESEARCH TRAINING
IN THE NORMAL AND DISORDER
PROCESSES OF HEARING, BALANCE,
TASTE, SMELL, VOICE, SPEECH, AND
LANGUAGE AND TO SUPPORT
BIOMEDICAL AND BEHAVIORIAL
RESEARCH THAT WILL IMPROVE THE
LIVES OF MILLIONS OF PEOPLE WITH
THESE DISORDERS.
THE BEYOND THE LAB'S LECTURE
SERIES IS AN OPPORTUNITY FOR
EVERYONE INSIDE AND OUTSIDE OF
THE NIH ADMINISTRATIVE STAFF,
SUPPORT STAFF, SCIENTISTS AND
THE PUBLIC TO LEARN ABOUT NIDCD
RESEARCH AND COMMUNICATION
DISORDERS.
CONDITIONS THAT SIGNIFICANTLY
AFFECT ABOUT 20% OF THE U.S.
ADULTS AT SOME POINTS IN THEIR
LIVES.
THIS SPEAKER SERIES IS PART OF
THE NIDCD'S ADMINISTRATIVE
STRATEGIC PLAN WHICH WORKS TO
BUILD AWARENESS AND IMPROVE THE
SERVICES THAT SUPPORT NIDCD'S
MISSION.
PLEASE NOTE THAT WE EXPECT TO
HAVE A FEW MINUTES AFTER THE
PRESENTATION FOR OUR SPEAK TORE
ANSWER YOUR QUESTIONS.
NOW AT THIS TIME, I WOULD LIKE
TO INTRODUCE DR. LISA
CUNNINGHAM, NIDCD'S SUPERB
SCIENTIFIC DIRECTOR.
SHE LEADS THE NIDCD DIVISION OF
INTRAMURAL RESEARCH WHICH
CONDUCTS BASIC AND CLINICAL
RESEARCH IN HUMAN COMMUNICATION.
DR. CUNNINGHAM WILL NOW
INTRODUCE TODAY'S SPEAKER AND
PLEASE JOIN ME IN WELCOMING
DR. CUNNINGHAM TO THE PODIUM.
NTHANK YOU MARK, GOOD AFTERNOON.
AND THANKS EVERYONE FOR JOINING
US TODAY.
IT IS MY DISTINCT PLEASURE TO
WELCOME YOU TO TODAY'S TALK ON
HOW KATIE KEINDT'S LAB TO
OBSERVE IN REALTIME HOW HAIR
CELLS CHANGE AND RESPOND TO THE
ENVIRONMENT EMPLOY AS MARK
MENTIONED, NIDCD DEVELOPED THIS
SPEAKER SERIES FOR PEOPLE WHO
MIGHT NOT HAVE TRAINING OR
SPECIFIC BACKGROUND IN SCIENCE.
OUR GOAL IS TO TAKE WHAT WE'RE
DISCOVERING IN THE LAB OR IN THE
CLINIC AND SHARE IT WITH BOTH
SCIENTIFIC AND NONSCIENTIFIC
STAFF AT NIH, INTERESTED
COMMUNITY MEMBERS, PATIENTS AND
THEIR FAMILIES, ADVOCATES AND
HEALTH PROFESSIONALS.
WE HOPE THAT SHARING SCIENTIFIC
ADVANCES ON DEAFNESS AND OTHER
COMMUNICATION DISORDERS HELPS
OUR STAFF AND THE COMMUNITY COME
AWAY WITH A GREATER
UNDERSTANDING OF HOW WE ARE
ADVANCING THE SCIENCE AND
ULTIMATELY HELPING PEOPLE WITH
COMMUNICATION CHALLENGES AND
THEIR FAMILIES.
WE ALL PLAY A ROLE IN IMPROVING
PUBLIC HEALTH.
AND NOW I WOULD LIKE TO TELL YOU
A LITTLE BIT ABOUT TODAY'S
SPEAKER, DR. KATIE KINDT,
DR. KINDT RECEIVED A DEGREE IN
BIOLOGY AND MOLECULAR CHEMISTRY
FROM WISCONSIN AND Ph.D. FROM
THE UNIVERSITY OF CALIFORNIA SAN
DIEGO WHERE SHE STUDIED FUNCTION
AND DEVELOPMENT OF MECH KNOW O
SENSORY ELEMENTS IN WORMS OF
C.ELEGANS.
DR. KINDT JOINED NIDCD AS AN
INVESTIGATOR IN 2013.
HERE LABORATORY WHICH IS CALLED
THE SECTION ON SENSORY CELL
DEVELOPMENT AND FUNCTION USES
MOLECULAR AND MICROSCOPY BASED
METHODS TO EXAMINE SENSORY CELL
FUNCTION AND DEVELOPMENT.
IT'S REALLY BEAUTIFUL WORK AS
YOU WILL SEE FROM HER TALK
TODAY.
DR. KINDT WILL SHARE HOW HER LAB
USES LIVE IMAGING TO OBSERVE
REALTIME HOW ZEBRAFISH HAIR
CELLS CHANGE AND RESPOND TO THE
ENVIRONMENT.
ZEBRAFISH ARE USING THE MODEL
SYSTEM FOR STUDYING HAIR CELLS
BECAUSE THEY'RE TRANSPARENT WHEN
THEY DEVELOP WHICH ALLOWS
DR. KINDT TO WATCH THE CHANGE
AND SEE IT AS IT MATURES, AND
THE SAME CHANGES IN HEARING LOSS
IN ZEBRAFISH ARE THE SAME TO
HUMANS, WE WE CAN EXTRACT THIS
TO HUMANS WITH CHANGES IN THEIR
HEARING.
KATIE ALWAYS GIVES A GREAT TALK
AND I ALWAYS LOVE HEARING HER
TALK, THANK YOU FOR JOINING US,
I HOPE YOU ENJOY TODAY'S TALK
AND NOW I WELCOME DR. KINDT.
>> ALL RIGHT THANKS SO MUCH FOR
THOSE INTRODUCTIONS.
IT WAS REALLY LOVELY.
IT'S GREAT TO SEE ALL OF YOU IN
PERSON TODAY.
I'VE BEEN MISSING THESE
IN-PERSON TALKS AND I AM EXCITED
TO HAVE THE OPPORTUNITY TO TALK
ABOUT THE RESEARCH GROUP IN MY
INTRAMURAL GROUP AT THE
PORTFOLIO PROGRAM AT THE NIDCD,
IN THIS BEYOND THE LAB SERIES
WHERE WE USE ZEBRAFISH TO HELP
US SEE HOW HEARING WORKS.
SO BEFORE I WE BEGIN I WANT TO
SHOW A PICTURE OF THE LAB
MEMBERS AND OUR GROUP, THIS IS
SENSORY DEVELOPMENT AND FUNCTION
AND WE'RE LOCATED IN BUILDING
35A AND THE FIRST FLOOR IN THE D
AREA SO IF YOU ARE EVER OVER AT
35, I WOULD ENCOURAGE YOU SO IF
YOU ARE INTERESTED IN LOOKING AT
MORE, PLEASE STOP BY, AND VERY
BROADLY SPEAKING, OUR LAB USES
ZEBRAFISH TO STUDY HUMAN OTHER
AND BALANCE.
SO HEARING IMBALANCE ARE SENSES
THAT TART IN OUR EAR WHICH I'LL
TELL YOU MORE ABOUT TODAY AND
GENERALLY WHEN I TELL PEOPLE
THIS, THAT I USE ZEBRAFISH TO
STUDY HEARING AND I GET A TERIO
TYPE QUESTION, AND MAYBE SOME OF
THESE QUESTIONS ARE GOING AROUND
IN YOUR HEAD RIGHT NOW.
SO THE FIRST THING THAT PEOPLE
ASK AFTER I SAY THIS IS THEY SAY
ZEBRAFISH?
AND I'M NOT SURE IF THAT'S A
QUESTION THERE BUT I PUT IT
THERE AND WHY DO YOU STUDY
ZEBRAFISH WHICH IS A GREAT
QUESTION.
BECAUSE I STUDY HEARING
IMBALANCE, THEY SAY WELL CAN
ZEBRAFISH HEAR?
AND IS IT RELEVANT TO STUDY IT?
I THINK LISA GAVE IT AWAY BUT I
WILL GO INTO MORE DETAIL.
AND
AND WHY NOT JUST USE ANOTHER
MODEL LIKE MOUSE OR PRIMATES OR
SOMETHING LIKE THAT.
AND LASTLY WHAT DO YOU EXACTLY
STUDY?
SO I WILL END BY GIVING ATH
SYNOPSIS WE'RE CURRENTLY
STUDYING IN THE LAB RIGHT NOW,
ALL RIGHT?
SO THESE QUESTIONS FOLLOWED WITH
MY ANSWERS WILL SORT OF FORM THE
OUTLINE OF MY TALK TODAY, SO
LET'S GO WITH THE FIRST
QUESTION: ZEBRAFISH, WHY DO YOU
STUDY ZEBRAFISH IN AND WHEN I
SAY ZEBRAFISH, WHAT I MEAN ARE
THESE BEAUTIFUL DANIOS, THESE
ARE STRIPED FISH, COMMON PET
STORE VARIETY YOU CAN FIND
ACROSS THE U.S. AND ACROSS THE
WORLD.
AND MANY DIFFERENT LABS ACROSS
THE NIH INCLUDING SUCH AS NIDCD
AND OTHER INSTITUTES USE
ZEBRAFISH AS AN ANIMAL MODEL FOR
RESEARCH.
AND WHY DO WE DO RESEARCH ON AN
IN ANIMAL MODELS.
WELL, UNFORTUNATELY, OR
FORTUNATELY, PERHAPS RESEARCH IN
HUMANS IS LIMITED.
SO WHAT I'M SHOWING YOU HERE IS
A PICTURE OF MY HUMAN AND
THERE'S ONLY SO MANY EXPERIMENTS
I WANT SCIENTISTS TO PERFORM
ON HIM, RIGHT, SO INSTEAD
SCIENTISTS USE A WIDE VARIETY OF
ANIMAL MODELS FOR RESEARCH, SO
HERE I'M SHOWING PRIMATES,
RODENTS, OUR FRIEND THE
ZEBRAFISH WHICH WE WILL TALK
ABOUT TODAY, DROSOPHILA AND THE
CELEGANCES TOADS WHICH I DID MY
Ph.D. ON.
AND SO WE USE THESE TO TODAY AND
MODEL HUMAN DISEASE AND APPLY
THE KNOWLEDGE WE LEARN FROM
THESE ANIMAL MODELS TO ENHANCE
HUMAN HEALTH.
AND OF ALL THE DIFFERENT ANIMAL
MODELS, EACH HAD ITS OWN UNICK
ADVANTAGES AND DISADVANTAGES FOR
RESEARCH.
AND TODAY I WILL TELL YOU ABOUT
ZEBRAFISH AND 1 OF THE MAIN
ADVANTAGES FOR ZEBRAFISH IS THAT
IT'S REALLY GREAT FOR STUDYING
DEVELOPMENT.
SO IF YOU THINK ABOUT
DEVELOPMENT IN MAMMALS LIKE
HUMANS, LIKE OURSELVES, OR EVEN
IN PRIMATES OR IN RODENTS, A LOT
OF THE DEVELOPMENT HAPPENS IN
UTTEREE AND IT MAKES IT CHAL
ERVELGING TO SEE WHAT'S
HAPPENING AS THE BABY'S
DEVELOPING.
SO MANY OF YOU ARE PERHAPS
FAMILIAR WITH HUMAN ULTRA SOUND,
MAYBE YOU'VE HAD 1 OR SEEN THEM
AND THEY'RE POWERFUL IMAGES BUT
THEY CAN ONLY TELL US SO MUCH
ABOUT WHAT'S HAPPENING DURING
DEVELOPMENT, THE GENDER OR
OVERALL HOW THINGS ARE
DEVELOPING, WE CAN'T REALLY GET
INSIDE AND SEE THE DETAILS OF
WHAT'S HAPPENING.
BUT IN CONTRAST IN MAMMALS, TO
ZEBRAFISH, DEVELOPMENT HAPPENS
EXTERNALLY, OUTSIDE OF THE
MOTHER.
SO WHAT I'M SHOWING ON THE
BOTTOM RIGHT IS AN ADULT
ZEBRAFISH, 3-CENTIMETERS LONG,
AND IN THE TRUSTEES IS A NEWLY
FERTILIZED ZEBRAFISH EMBRYO, SO
WHAT WE DO IN THE LAB, IS WE
TAKE ADULT ZEBRAFISH, AND WE PUT
THE MALE AND FEMALE TOGETHER IN
THE BREEDING TANK AND THE FEMALE
WILL RELEASE HER EGGS AND THE
MALE COMES ALONG AND RELEASE THE
SPERM AND IT HAPPENS IN THE
WATER AND WE CAN COLLECT THE
EMBRYOS TO LOOK AT THEM AND SEE
HOW THEY DEVELOP.
SO JUST TO GIVE YOU SOME CONTEXT
BEFORE I PLAY THIS MOVIE.
SO THIS IS THE CELL WHERE THE
NEWLY FERTILIZED EMBRYO WILL
FORM AND THIS BELOW IS THE YOLK
THAT WILL FEED THE EMBRYO AND
AROUND THE EMBRYO IS THE EGG
SHELL OR CORRIAN, SORT OF LIKE
THE BUBBLE THAT CURBONS THE
EMBRYO.
YOU CAN'T SEE THE POINTERS?
THERE YOU GO.
TECHNOLOGY FAILED.
THANK, GUYS.
SO AS WE WATCH THIS MOVIE THIS
WAS AN EMBRYO THAT JUST
COLLECTED BUT WITHIN AN HOUR THE
SINGLE CELL ON TOP WILL DIVIDE
TO FORM THE NEW ZEBRAFISH
EMBRYO, AND I HOPE YOU CAN
APPRECIATE THAT AS LISA
MENTIONED, ZEBRAFISH ARE
TRANSPARENT AT THESE YOUNGER
AGES SO WE CAN WATCH EACH AND
EVERY CELL DIVISION HAPPEN AND
EVERY MORCH LOGICAL EVENT THAT
HAPPENS AS THIS EVENT IS
DEVELOPING.
SO WHAT I'LL BE SHOWING YOU IN
THE FIRST SEGMENT IS THE FITTER
24 HOURS OF ZEBRAFISH
DEVELOPMENT SO AS YOU CAN SEE
THE CELLS START BECOMING SMALLER
AND SMALLER AS THEY DIVIDE MORE,
AND THEN WE GET TO SEE THESE
EXTRAORDINARY MORPHOLOGICAL
CHANGES THAT HAPPENS AND THEN
NOW, BEGINNING TO SEE THE
ZEBRAFISH HEAD FORMING HERE AND
THE TAIL, SO THIS IS EYE OF THE
ZEBRAFISH HERE AND SO THIS IS
THE FIRST 24 HOURS OF
DEVELOPMENT AND THE MUSCLE BANDS
ARE FORMING ALONG THE BODY, IT'S
NOW ABLE TO MOVE IN JUST 24
HOURS, SO HERE'S 2 DAYS, IT'S
DEVELOPING EVEN MORE, IT'S MORE
ACTIVE, AND THEN AFTER 3 DAYS,
THE LITTLE SLOW DOWN, IS ABOUT
READY TO HATCH ALREADY.
AND AS SOON AS IT HATCHED, IT
WILL BECOME A FREE SWIMMING
ZEBRAFISH, WHICH IS
EXTRAORDINARY ALL WITHIN 3 DAYS.
SO HERE'S A LITTLE FREE SWIMMING
ZEBRAFISH AND ALTHOUGH WE DO
STUDY ADULT ZEBRAFISH FOR SOME
OF OUR RESEARCH, THE MAJORITY WE
DO IS ACTUALLY IN THE EARLY
EMBRYOS OR NEWEL HATCHED LARVA
WE CALL THEM AND THAT'S BECAUSE
THEY'RE TRANSPARENT AS THESE
YOUNG AGES AND WE CAN SEE THINGS
HAPPENING REALLY WELL.
AND THERE ARE OF COURSE OTHER
REASONS WHY, THIS IS A GREAT
MODEL AND I COULD GO ON ALL DAY
ABOUT IT BUT LET'S GIVE YOU A
FEW MORE REASONS SO THEY
DEVELOPED EXTERNALLY, THEY'RE
TRANSPARENT AT THIS YOUNG AGES,
THEY'RE BONY FISH SO IT'S A
VERTEBRATE MODEL AND THERE'S
GREATER GENETIC CONSERVATIONS
COMPARED TO OTHER INVERTEBRATE
MODELS PEOPLE STUDY IN ADDITION
IF YOU THINK ABOUT GETTING A PET
FISH FOR YOUR KIDS, ZEBRAFISH
ARE PRETTY EASY TO MAINTAIN AT
HOME AND IN THE LAB SO THAT
MAKES THEM A PRETTY GOOD MODEL
TO STUDY, AND IF WE SET UP A
PAIR OF ADULT ZEBRAFISH, THEY
WILL LAY HUNDREDS OF THOSE
EMBRYOS EACH WEEK FOR US TO
STUDY, WHICH THEY'RE VERY
PROLIFIC, IT'S PRETTY
EXTRAORDINARY.
AND IF I DON'T KNOW IF ANY OF
YOU WORK ON MICE, YOU DON'T EVER
GET A HUNDRED PUPS IN YOUR
LITTER.
YOU KNOW?
, YEAH.
SO THOSE ARE SOME OF THE REASONS
THAT ZEBRAFISH HAS NOW BECOME A
WIDELY USED ANIMAL MODEL FOR
RESEARCH.
SO ZEBRAFISH, YES, I STUDY
ZEBRAFISH AND WE STUDY BECAUSE
IT'S A GREAT MODEL TO STUDY
DEVELOPMENT.
SO PEOPLE ASK CAN ZEBRAFISH HEAR
IN AND THE YES IS YES, THEY CAN
HEAR.
AND THE EASIEST WAY TO TELL IF
YOU HAVE A ZEBRAFISH THAT'S DEAF
OR NOT IS TO DO AN ACOUSTIC
STARTLE RESPONSE.
IT'S A CONSERVED BEHAVIORIAL
REACTION, OR A SUDDEN AND
AUTOMATIC RESPONSE TO A LOUD
SOUND.
SO I FOUND THIS VIDEO OF A
HUNDRED DIFFERENT PEOPLE ON THIS
WEBSITE WHERE THEY DO A HUNDRED
THINGS TO A HUNDRED PEOPLE AND
THEY RECORD THEIR RESPONSES OR
WHATEVER AND I'M NOT GOING TO
SHOW, I WON'T SHOW A HUNDRED
PEOPLE'S RESPONSE, BUT THEY
POPPED A BALLOON AND RECORDED
THE AUTOMATIC RESPONSE TO THIS
LOUD NOISE.
BUT I WAS PRETTY ENTERTAINED BY
WATCHING THE VIDEO.
THERE'S NO AUDIO BECAUSE THERE'S
LOTS OF SWEARING.
[LAUGHTER]
SO ZEBRAFISH RESEARCH ARES DO
SOMETHING SIMILAR IN THE LAB
EXCEPT FOR OF COURSE, BECAUSE WE
DON'T POP A BALLOON BECAUSE THEY
LIVE IN THE WATER AND THEY DON'T
HEAR IN THE AIR AS WELL, SO WE
HAVE TO GET THE SOUND TO TRAVEL
THROUGH THE WATER, SO THIS IS AN
EXAMPLE OF AN ASSAY WE DO IN THE
LAB SO JUST TO GIVE YOU CONTEXT
THIS, IS A 10-CENTIMETER PETRI
DISH AND HERE'S A PENNY DOWN
HERE FOR CONTEXT AND IN THE
CENTER IN THIS BOX IS A SINGLE
ZEBRAFISH, IT'S 5 DAYS OLD, IT'S
VERY SMALL, YOU KNOW?
AND TO DELIVER THE CELL
STIMULUS, WE CAN TAP THE--SOUND
STIMULUS, WE CAN TAP THE
EPI-BLAST EDGE OF THE DISH, SO
WE PLAY THE MOVIE SO WATCH THE
STIMULUS, SO AFTER THE RESPONSE
TO THE TAP, YOU WILL SEE THE
SOUND WAVE TRANSFER FROM THE
EDGE TO THE CENTER, AND YOU CAN
SEE THE SOUND TRAVELING THROUGH
WATER WHICH IS PRETTY COOL.
I WILL PLAY THE MOVIE AGAIN BUT
I WANT YOU TO FOCUS IN ON THIS
LITTLE ZEBRAFISH MOVIE AGAIN, SO
NOW THE ZEBRAFISH TURNS AND
START SWIMMING AWAY, SO IT'S
TRYING TO ESCAPE FROM THE LOUD
SOUND THAT IT HEARD AND THAT'S
ITS VERSION OF THE ACOUSTIC
STARTLE RESPONSE AND THIS
RESPONSE IS PRESENT WHEN THE
ZEBRAFISH IS ONLY 5 DAYS OLD
WHICH IS PRETTY EXTRAORDINARY.
ALL RIGHT, SO CAN ZEBRAFISH
HERE, YES THEY CAN, FOR EXAMPLE,
THEY CAN RESPOND TO LOUD SOUND
IN THIS ACOUSTIC RESPONSE AS
WELL AS OTHER SOUNDS IN WATER.
BUT IS IT RELEVANT TO STUDY
HUMAN HEARING IN ZEBRAFISH?
AND THE MAIN WAY THAT
RESEARCHERS DEMONSTRATED THE
RELEVANCE OF ZEBRAFISH TO STUDY
HUMAN HEARING IS THROUGH
EXPERIMENTS THEY DID TO FISH
REALLY OR IDENTIFY REQUIRED NEW
GENES FOR HEARING.
AND 1 WAY RESEARCHERS LOOK FOR
NEW GENES IS SOMETHING CALLED
THE GENETIC SCREEN AND THIS IS
WHERE YOU TAKE YOUR ANIMAL MODEL
AND YOU CREATE A BUNCH OF RANDOM
MUTATIONS IN THEIR DNA IN
DIFFERENT GENES, ALL SORTS OF
DIFFERENT GENES AND MAYBE NO 1
KNOWS ABOUT BUT THE--BUT YOU
LOOK FOR SCIENTIFIC TRAITS.
IN SOME WAYS, WHEN I THINK ABOUT
DOING THIS, I FEEL LIKE I'M KIND
OF A MAD SCIENTIST, YOU KNOW
WHAT I MEAN?
LIKE SOMETHING OUT OF A COMIC
BOOK THEORY, OR YOU HAVE TEENAGE
MUTANT ININ JAMILA TURTEMS OR
YOU HAVE TURTLES WALKING THROUGH
RADIOACTIVE OOZE AND THEN OF
COURSE CHANGE.
WE DON'T HAVE RADIO ACTIVE OOZE,
I DON'T KNOW WHAT THAT WOULD
LIKE LIKE FROM MY PROTOCOL BUT
INSTEAD WE HAVE A CHEMICAL MUTA
GENERATED THAT DISRUPTS DNA AND
WHEN I INCUBATED ZEBRAFISH AND
THE MUTA GENERATED HAVE NEVER
SEEN ANY TEENAGE MUTANT
ZEBRAFISH EVER, I DON'T EVEN
KNOW IF IT'S POSSIBLE AND OF
COURSE THE VENE WORKS
DIFFERENTLY, WE NEVER DIRECTLY
TRANSFORM A FISH INTO A MUTANT
FISH.
WE ARE MUTATING THE GAMETES OR
THE EGG, THE SPERM OF THE ADULLS
AND THEN WE'RE LOOKING AT THE
PROGENY FOR A SPECIFIC TRAIT
THAT WE'RE INTERESTED IN AND
WHAT RESEARCHERS HAVE DONE WITH
REGARDS TO HEARING AND BALANCE
FIELD IS THE SPECIFIC TRAIT THEY
KREENED FOR IS DEAF MUTANT
ZEBRAFISH AND THEY DID THIS
USING THE ACOUSTIC STARTLE ASSAY
I JUST SHOWED YOU.
SO HERE'S AN EXAMPLE OF 1 OF
THESE DEAF MUTANT ZEBRAFISH, NOT
A NINJA.
AND IN THIS CASE, IF WE TAP THE
DISH, IF YOU FOCUS IN ON THIS
FISH, YOU WILL SEE THE SOUND
WAVE LIKE MOVING TOWARDS THE
FISH AT THE END OF THE VIDEO BUT
THE FISH NEVER MOVES IN RESPONSE
TO THE STIMULUS, THAT'S BECAUSE
IT'S UNABLE TO HEAR.
IT WAS REALLY INTERESTING ABOUT
THE SCREEN WAS IN ADDITION TO
BEING DEAF, MANY OF THESE FISH
ALSO SHOWED DISORIENTED MOVEMENT
SO THEY WOULD LAY ON THEIR
SIDES, THEY WOULDN'T SWIM
UPRIGHT LIKE A NORMAL FISH AND
IF THEY DID MOVE, THEY WOULD
MOVE IN A VERY UNCORDINATED
MANNER AND SOMETIMES THEY WILL
SWIM IN CIRCLES, WHICH INDICATE
THAT NOT ONLY DID THEY NOT HEAR
BUT THEY ALSO HAD PROBLEMS WITH
BALANCE AND THIS IS INTERESTING
BECAUSE THIS MOVEMENT IS ALSO
HOW FISH BEHAVE IN SPACE.
SO THIS IS A MOVIE FROM THE
CHINESE SPACE STATION FROM EARLY
EARLY THIS MONTH WHERE THEY
LAUNCHED 4 ADULT ZEBRAFISH INTO
OUTER SPACE TO STUDY FOR VARIOUS
REASONS AND WHAT THE NEWSCASTERS
ARE SAYING IN THIS RECORDING IS
THAT THESE ADULT ZEBRAFISH WERE
SWIMMING VERY DISORIENTEDLY,
THEY'RE SWIMMING IN ALL
DIFFERENT DIRECTIONS AND CIRCLES
BECAUSE THEY DON'T KNOW WHICH
WAY IS UP.
BECAUSE THAT'S BECAUSE THEY USE
THEIR EAR TO SENSE GRAVITY, TO
BE ABLE TO SWIM UPRIGHT AND IN
SPACE, THERE'S NO GRAVITY WHICH
IS QUITE COOL.
SO BECAUSE OF THE SIMILARITIES
BETWEEN THE DEAF MUTANT FISH IN
FISH AND SPACE, THESE AQUANAUTS,
WITH THESE ASTRONAUTS THEY
ORIGINALLY GAVE THEM ALL SPACE
NAMES LIKE SPUTNIK AND
SATELLITE, MERCURY, STAR DUST
BECAUSE THEY DIDN'T KNOW WHICH
CHIENS HAD MUTATED SO IT'S A
THING THAT PEOPLE WITH GENETIC
STRINGS DO, IT'S AWESOME BUT AS
TIME WENT ON, THEY SEQUENCED THE
DNA OF THESE DIFFERENT DEAF
MUTANT ZEBRAFISH AND THEY FOWBD
THAT MANY OF THE GENES WHICH ARE
ALL LISTED HERE, WERE
ACTUALLY--WHEN MUTATED NOT ONLY
CAUSED HEARING LOSS IN ZEBRAFISH
BUT ALSO CAUSED HEARING LOSS IN
HUMANS SO I LISTED ALL THESE
LOCI THAT CAUSE DEAFNESS IN
HUMANS AND IN SOME CASES IT WAS
REQUIRED THAT ONLY SOME OF THESE
ARE REQUIRED FOR HEARING AND
IMAL BALANCE WHICH IS QUITE
EXTRAORDINARY.
AND OVERALL THIS DID DEMONSTRATE
THAT, OR THIS GENETIC
CONSERVATION DEMONSTRATE TODAY
WAS A VERY RELEVANT MODEL TO
STUDY HEARING AND BALANCE.
SO IS IT RELEVANT TO STUDY HUMAN
HEARING IN ZEBRAFISH?
IT'S VERY COOL.
SO ALTHOUGH IT'S RELEVANT, WHY
USE ZEBRAFISH?
IT'S ALSO RELEVANT TO STUDY
HEARING IMBALANCE IN MICE OR
OTHER MODELS SO WHAT'S GREAT
ABOUT USING ZEB RAW DATA FISH
FOR RESEARCH AND IN ORDER TO
EXPLAIN THIS I NEED TO TAKE A
STEP BACK AND TELL YOU A LITTLE
BIT ABOUT HUMAN HEARING.
SO HUMAN HEARING STARTS IN OUR
EARS, SO MANY OF YOU ARE
FAMILIAR WITH THE OUTER HERE,
BUT ULTIMATELY SOUND TRAVELS
FROM THE OUTER EAR INTO THE
INNER EAR CANAL AND TO A SPECIAL
PLACE CALLED THE INNER EAR WHICH
IS SHOWN HERE.
INSIDE THE INNER EAR ARE REALLY
SPECIAL CELLS CALLED SENSORY
HAIR CELLS, THAT FUNCTION AND
DETECT SOUND AND ALSO GRAVITY.
AND THESE ARE VERY--THESE ARE
DISTINCT FROM THE HAIRS ON OUR
HEAD BUT THEY GET THIS NAME
BECAUSE THEY HAVE THESE ADORABLE
TINY LITTLE HAIR LIKE
PROJECTIONS ON TOP OF CELL SO
THEY'RE CALLED HAIR CELLS.
BUT IN MEDICARE MAMMALS LIKE OR
HUMANS, THE INNER EAR IS
ACTUALLY SURROUNDED BY 1 OF THE
DENSEST BONES IN THE BODY SO IF
WE WANT TO STUDY THESE CELLS, WE
HAVE TO ACTUALLY REMOVE THE EAR.
AND THEREFORE, IT'S REALLY
CURRENTLY NOT POSSIBLE TO STUDY
THESE CELLS IN A LIVING ANIMAL
IN MAMMALS, BUT IN CONTRAST, WE
THINK ABOUT OUR TRANSAPPARENT
ZEBRAFISH, IT IS POSSIBLE TO
SIMPLY LOOK INSIDE THE EAR AND
LOOK AT ITS HAIR CELLS, SO
THEY'RE SHOWING YOU HERE IS A 5
DAY OLD ZEBRAFISH, MOUNTED HERE,
SO IT'S BELLY'S DOWN, AND I HOPE
YOU CAN APPRECIATE, THIS IS A
ZEBRAFISH HERE WHICH I WILL TELL
YOU MORE ABOUT AND WE CAN SIMPLY
LOOK IN AND SEE WHAT'S HAPPENING
WITHOUT ANY KIND OF DISSECTION
OR-YEAH.
AND WHAT'S ALSO REALLY POWERFUL
ABOUT BEING A TRANSPARENT ANIMAL
IS THAT WE CAN USE USE OTHER
REALLY COOL WILL TOOLS FOR OUR
EXPRCH 1 FORT COOLEST IS GREEN
FLUORESCENT PROTEIN OR GFP.
AND GREEN FLOURESCENT PROTEIN IS
A PROTEIN THAT WAS ORIGE
NAWILLLY IDENTIFIED IN JELLY
FISH, SO RESEARCHERS FOUND THAT
A CERTAIN TYPE OF JELLY FISH
WHEN YOU SIGN BLUE LIGHT ON IT,
IT GLOWS GREEN WHICH IS PRETTY
EXTRAORDINARY AND THEN THEY WERE
THOUGHTFUL ENOUGH TO IRS DEBTIFY
THE GENE AND THE PROTEIN THAT
WAS INVOLVED IN MAKING JELLY
FISH GLOW, GFP AND THEN THEY DID
ALL SORTS OF FUN THINGS WITH THE
MOLECULE AND 1 THING THEY DID
WAS MAKE TRANSGENIC ANIMALS AND
TRANSGENIC ANIMAL IS JUST AN
ORGANISM WHERE YOU'VE TAKEN A
GENE SUCH AS GFP FROM ANOTHER
SPECIES AND ADD IT TO ANOTHER
ORGANISM, SO FOR EXAMPLE, TAKING
GFP FROM JELLY FISH AND PUTTING
IT INTO ZEBRAFISH WILL GIVE US A
TRANSGENIC ZEBRAFISH.
SO A LOT OF PEOPLE HAVE MADE ALL
SORTS OF GPP ANIMALS YOU CAN
FIND CAT, CHICKEN, YOU NAME IT
OUT THERE AND THAT'S SOME OF THE
FIRST TRANSGENIC ANIMALS WERE
ACTUALLY GLOW FISH.
AND SOME OF THE VERY FIRST WERE
ACTUALLY HERE, ZEBRAFISH, IN THE
SKIN AND I WAS AMUSED YOU COULD
GO ON AMAZON.COM AND BUY TBLOA
FISH OR TETRA'S, AND ALL THAT.
IN OUR LAB WE MAKE TRANSGENIC
ZEB RAW DATA FISH, NOT WITH
GLOWING SKIN, BUT INSTEAD WE
MAKE IT WITH GFP IN THE HAIR
CELLS SO WE CAN VISUALIZE THEM
BETTER.
SO THIS IS A 5 DAY OLD ZEBRAFISH
MOUNT OFFICE OF DIVERSITY THE
SIDE AND IF WE SIGN A LIGHT ON
IT WE CAN SEE ALL THE HAIR CELLS
IN GREEN WHICH IS QUITE COOL AND
THIS HELPS US IDENTIFY AND SEE
HAIR CELLS THAT WE CAN STUDY
THEN IN THIS LIVING ZEBRAFISH.
SO WOOK LOOKED CLOSER AT THE
HAIR CELLS IN ZEBRAFISH, THEY
HAVE AIR CELLS IN 2 MAIN SENSORY
SYSTEMS THAT I WILL TELL YOU
ABOUT, THE FIRST 1 IS A
ZEBRAFISH HERE WHICH IS SHOWN
HERE IN THIS BOX.
AND IF WE LOOK A LITTLE BIT
CLOSER, HIGHER AGNIFICATION AT 1
OF THESE CLUSTERS AND CELLS IS
WHAT IT LOOKS LIKE HERE AND I'VE
OUTLINED A SINGLE CELL HAIR HERE
WITH I DASH LINE AND ZEBRAFISH
USES HAIR CELLS IN THEIR EAR FOR
HEARING AND SO FOR THAT ACOUSTIC
STARTLE RESPONSE I SHOWED YOU
AND I ALSO USE IT FOR BALANCE TO
DETECT GRAVITY AND MAINTAIN
UPRIGHT POSTURE AND HAVE NORMAL
SWIMMING BEHAVIOR, BUT MAYBE YOU
CAN SEE THAT OUTSIDE OF THOSE
ZEBRAFISH HERE THERA'S A BUNCH
OF GREEN DOTS AS WELL.
AND THAT'S BECAUSE THEY HAVE
SOMETHING WE DON'T HAVE WHICH IS
QUITE COOL WHICH IS ANOTHER
SENSORY SYSTEM CALLED THE
LATERAL LINE, SO, THE LATERAL
LINE IS MADE UP OF ALL
THESE--ALL OF THESE LITTLE DOTS
THAT PROJECT IN LINES ON THE
FISH BODY AND EACH LITTLE DOT IS
ALSO A CLUSTER OF THESE SENSORY
HAIR CELLS, WHICH IS SHOWN HERE
IN THE BOTTOM LEFT, AND AGAIN,
I'VE OUTLINED 1 OF THESE HAIR
CELLS HERE THAT EXPRESSES GFP.
AND WHAT'S REALLY AMAZING FROM A
RESEARCH PERSPECTIVE IS THAT
THESE SENSORY HAIR CELLS IN THE
LATERAL LINE ARE LOCATED
DIRECTLY ON THE SURFACE OF THE
FISH SKIN, RIGHT ON THE SURFACE.
AND IF YOU COMPARE THIS TO THE
MAMMALIAN INNER EAR WHERE WE
HAVE HAIR CELLS EMBEDDED IN 1 OF
THE DENSEST BONES OF OUR BODY,
THE CONTRAST WITH REGARD TO THAT
STABILITY IS XREELLY EXTREME.
THE FISH IS LITERALLY GROWING
HAIR CELLS ON ITS SKIN FOR US TO
STUDY.
IT'S PRETTY AMAZING.
AND ZEBRAFISH AND OTHER AQUATIC
VERTEBRATES USE THEIR LATERAL
LINE TO SENSE LOCAL WATER
MOVEMENTS IN THEIR ENVIRONMENT,
BECAUSE THEY'RE A FISH, WHICH IS
PRETTY COOL AND IT GIVES THEM
SORT OF A SENSE OF LIKE TOUCH AT
A DISTANCE, RIGHT?
AND IT'S IMPORTANT FOR A LOT OF
BEHAVIORS FOR FISH, LIKE
BREEDING AND PREY DETECTION AND
PREDATOR AVOIDANCE AND SOME FISH
USE OUR LATERAL LINE FOR A COOL
BEHAVIOR CALLING, I'M SURE YOU
HAVE SEEN PRETTY COOL VIDEO ON
THIS, YOU CAN GO ON YouTUBE
AND WATCH THESE, BUT THIS IS THE
SARDINES THAT ARE SCHOOLING AND
THEY'RE USING THEIR LATERAL LINE
TO STAY CLOSE TO 1 ANOTHER BUT
NOT RUN INTO EACH OTHER WHEN
THEY ESCAPE FROM A PREDATOR, AND
HERE WE HAVE A SHARK TRYING TO
GET THEM.
AND THE SHOCKER HAS A LATERAL
LINE TOO BUT IT'S USING IT TO
DETECT ITS PREY.
SO WHY ARE ZEBRAFISH SO USEFUL
FOR HEARING IMBALANCE RESEARCH?
ONE REASON IS THAT WE CAN STUDY
SENSORY HAIR CELLS IN THIS
LIVING ANIMAL SO USING
TRANSPARENCY AND LIGHTING UP
CELLS FOR EXAMPLE, USING GFP.
AND NOW THAT I'VE TOLD YOU SOME
OF THE REASONS WHY ZEBRAFISH IS
SUCH AN EXTRAORDINARY MODEL AND
SOME OF THE ADVANTAGES AND TOOLS
THAT WE HAVE ON HAND TO USE
ZEBRAFISH FOR RESEARCH, I WILL
GIVE YOU AN EXAMPLE OF A
SPECIFIC PROJECT THAT'S
CURRENTLY GOING ON IN THE LAB
USING THESE TOOLS AND
ADVANTAGES.
AND THIS HAS TO DO WITH THOSE
SENSORY HAIR CELLS, SO, ON THE
LEFT, IS A SCHEMATIC OF 1 OF
THESE SENSORY HAIR CELLS SO HERE
ARE THESE LITTLE HAIR LIKE
PROJECTIONS ON THE TOP AND NOT
ONLY DID HAIR CELLS HAVE THEIR
HAIRS ON THE TOP BUT THEY ALSO
HAVE A SPECIAL CONNECTIONS AT
THE BOTTOM OF THE CELL THAT THEY
USE TO SEND SOUND SIGNALS TO THE
BRAIN.
SO WHEN HAIR CELLS ARE
ACTIVATED, IT DEFLECTS THESE
LITTLE HAIRS AND CAUSES THESE
CONNECTIONS TO RELEASE CHEMICALS
TO SIGNAL TO NEURONS AND
TRANSMIT THIS INFORMATION TO THE
BRAIN.
AND IN HAIR CELLS THESE
CONNECTIONS ARE RIBBONS, I
COULDN'T THINK OF HOW TO SAY IT
BUT THATALLY ACTUALLY WHAT
THEY'RE CALLED AND SO WE WILL
CALL THEM RIBBONS SO WE KNOW
THOSE CONNECTIONS OR RIBBONS ARE
IMPORTANT FOR HEARING, AND STUDY
VS SHOWN WHEN THESE CONNECTIONS
ARE LOST AFTER A LOUD NOISE,
SIMPLY AS WE AGE, UNFORTUNATELY
AND AFTER EAR TOXIC DRUGS, WE
CAN LOSE THESE CONNECTIONS AND
WHEN WE LOSE THESE CONNECTIONS
IT ACTUALLY IMPAIRS SIGNALING TO
THE BRAIN AND DISRUPTS HEARING.
SO 1 OF THE GOALS IN OUR LAB IS
TO UNDERSTAND HOW THESE
CONNECTIONS FORM AND IT'S OUR
HOPE THAT IF WE CAN UNDERSTAND
HOW THESE CONNECTIONS FORM
NORMALLY, WE CAN UNDERSTAND HOW
TO REFORM THEM AFTER THEY'RE
LOST IN THESE CASES OF HEARING
LOSS.
AND THIS IS WORK DONE BY A
SCIENTIST IN THE LAB
SAMAN HUSSAIN.
I WILL SHOW YOU A BIT ABOUT HER
WORK ON THIS TODAY.
SO WHAT SHE'S DONE IS SHE'S USED
LIVE IMAGING TO UNDERSTAND THIS
PROCESS IN MORE DETAIL AND I'M
SHOWING YOU HERE ARE 2 IMAGES OF
INDIVIDUAL HAIR CELLS AT THE
LEFT IS THE HAIR CELL AT 1 OF
THE EARLIEST STAGES ANDOT RIGHT
IS THE HAIR CELL THAT'S MATURE,
AND HERE, IN THIS IMAGE, ON
THESE IMAGES, THE HAIR CELLS
OUTLINED IN GREEN WITH GREEN
FLUORESCENT PROTEIN AND THOSE
RIBBONS, WAS DEVELOPING
CONNECTIONS ARE SHOWN--IT'S A
RED FLUORESCENT PROTEIN BUT IT'S
SHOWING HERE MAGENTA AND
HOPEFULLY YOU CAN APPRECIATE IN
THE LEFT IMAGE IS THAT WE HAVE A
BUNCH OF SMALL RIBBONS
THROUGHOUT THE CELL BUT LATER
ONCE THE HAIR CELLS MATURE, WE
HAVE JUST 3 OF THESE CONNECTION
ANDS THEY'RE AT THE BOTTOM OF
THE CELL, SO HERE'S THE TOP OF
THE SALE AND HERE'S THE BOTTOM
OF THE CELL AND ALTHOUGH THESE
SNAPSHOTS ARE REALLY IMPORTANT
WE ARE KIND OF MISSING SOME OF
THE STEPS IN BETWEEN, SO IF YOU
SAY I STUDIED DEPRIVATIONMENT
AND THIS IS WHAT HAPPENS, YOU
WOULD MISS A LOT OF INFORMATION.
IT'S SORT OF LIKE, I WENT TO THE
SOCCER GAME AND I WAS THERE AT
THE START, SO THIS IS WOMAN'S
WORLD CUP FROM LAST YEAR WHICH
WAS EXCITING, 0-0, AND THEN AT
THE END IT WAS 1-0, SPAIN WON.
SO YOU WOULD WANT TO KNOW MORE
THAN THE BEGINNING AND END, WELL
WHO SCORED, WHEN DID THEY SCORE?
NO GOAL?
PENALTY?
WHAT HAPPENED?
SO YOU CAN LOOK AT HIGHLIGHTS
AND YOU CAN GO BACK AND GO
THROUGH THE HIGHLIGHTS SO CAN
YOU SEE THAT [INDISCERNIBLE]
CARMONA, SCORED A GOAL, BUT IT
DOESN'T TELL YOU THE WHOLE
STORY.
IT GIVES YOU ANOTHER PIECE.
SO THE STAIM THING IS TRUE WHEN
STUDYING DEVELOPMENT.
WE CAN OF COURSE GET A HIGHLIGHT
SO WE CAN LOOK AT A STEP IN
BETWEEN THE START OF THE GAME
AND THE END OF THE GAME AND WE
STILL DON'T REALLY KNOW WHAT
HAPPENED, RIGHT?
SO WHAT YOU HAVE TO DO IS WATCH
THE WHOLE GAME, RIGHT?
AND THE WAY WE CO THIS IS TO
MAKE MOVIES TO SEE HOW IT
HAPPENS.
SO MAKING MOVIES WE WERE ABLE TO
ANSWER 2 MAIN QUESTIONS WITH
REGARD TO THIS PROCESS.
ONE, HOW DO ALL THESE LITTLE
RIBBONS GET TO THE BOTTOM OF THE
CELL, LIKE THEY ARE DOWN HERE?
AND ALSO HOW DO THESE TINY
LITTLE BABY RIBBONS ULTIMATELY
GET BIGGER?
WHAT SOMEONE FOUND FROM MAKING
MOVIES IS THAT RIBBONS MOVE TO
THE BOTTOM OF THE CELL THROUGH
SPECIALIZED CELLULAR HIGH WAYS
AND HERE ON THE LEFT IS A MOVIE
SHOWING GFP LABELED HIGHWAYS AND
MIGHT BE MICROTUBULES ON THE
RIGHT I'M JUST SHOWING YOU 1
CELL HERE, SO THIS IS THE TOP OF
THE HAIR CELL AND THIS THE
BOTTOM OF THE HAIR CELL AND I
HOPE YOU CAN APPRECIATE THAT
THERE'S THESE LONG FILAMENTS,
THEY'RE VERY DYNAMIC BUT THEY
EXTEND FROM THE TOP TO THE
BOTTOM IN THE CELL AND WE ALSO
MADE MOVIES SHOWING THAT THESE
RIB
RIBBONS CAN MOVE ALONG THESE
HIGHWAYS TO MOVE ALONG THE TOP
AND BOTTOM OF THE CELL, WHICH IS
QUITE COOL. AND WITH REGARD TO
THE SECOND QUESTION, HOW DO BABY
RIBBONS GET BIGGER WE FOUND THAT
SMALL RIBBONS CAN FUSE TOGETHER
DURING DEVELOPMENT TO CREATE
LARGER 1S.
SO ON THE LEFT IS A SINGLE HAIR
LINE AND I'M SHOWING YOU 2
RIBBONS HERE THAT ARE OUTLINED
WITH THESE ARROWS AND I'VE BLOWN
THEM UP ON THE RIGHT HERE AND IF
I PLAYED THIS MOVIE, YOU CAN SEE
THESE 2 RIBBONS ACTUALLY FUSE
TOGETHER ON THE MICROTUBE YULE
HIGHWAY TO FORM LARGER RIBBONS.
HERE WE GO.
SO BY USING MOVIES WE'RE ABLE
TOW LIKE REALLY TELL THE WHOLE
STORY AND BEGIN TO PIECE
TOGETHER WHAT'S HAPPENING DURING
THIS DEVELOPMENTAL PROCESS, SO
HOW DO THE RIBBONS GET TO THE
BOTTOM, THEY MOVE ALONG THESE
MIKE RADIO TUBULE HIGHWAYS TO
REACH THE BOTTOM AND HOW DO
THOSE LITTLE BABY RIBBONNINGS
GET BIGGER, WELL, THEY FUSE
TOGETHER TO BECOME LARGER.
AND WE MIGHT HAVE BEEN ABLE TO
GUESS THIS BUT, LIKE, SEEING IS
BELIEVING, WE CAN'T GUESS, WE
ARE SCIENTISTS WE HAVE TO KNOW
WHAT HAPPENS.
SO, BY UNDERSTANDING THE
FUNDAMENTALS OF WHAT HAPPENS
DURING THESE DEVELOPMENTAL
PROCESS, IT'S REALLY IMPORTANT
BECAUSE IT PROVIDES US
INFORMATION THAT WE NEED TO
ACTUALLY REFORM THESE
CONNECTIONS AFTER THEY ARE LOST
IN CASES OF HEARING LOSS.
AND SO BEFORE I END, I WANT TO
END WITH TAKE HOMES THAT I WENT
THROUGH TODAY, SO ZEB RAW DATA
FISH, YES, WHY DO YOU STUDY
ZEBRAFISH?
BECAUSE IT'S AN EXTRAORDINARY
MODEL TO SEE DEVELOPMENT
HAPPENING.
I'VE TOLD YOU TODAY ABOUT HAIR
CELL DEVELOPMENT BUT OTHER LABS
USE ZEB RAW DATA FISH TO STUDY
EYE DEVELOPMENT, HEART
DEVELOPMENT, SPINAL CORD
DEVELOPMENT IT'S AN
EXTRAORDINARY MODTO SEE HOW
THINGS FORM.
CAN ZEBRAFISH HEAR, YES, YES,
THEY CAN HEAR.
THEY CAN RESPOND TO SOUND, WAVES
AND WATER, FOR EXAMPLE, IN THE
ACOUSTIC STARTLE RESPONSE, AND
FURTHER MORE, DEAF FISH BEHAVE
LIKE FISH IN SPACE WHERE THEY
CAN'T--THEY ACT LIKE THEY CAN'T
SENSE GRAVITY AND THEY HAVE
DISORIENTED SWIMMING.
IS ZEBRAFISH RELEVANT TO STUDY
HUMAN HEARING?
YES, SO MANY OF THOSE DEAF FISH
WHICH RESEARCHERS IDENTIFY THE
GENE LESIONS SHOWED THAT THE
SAME GENES ARE REQUIRED FOR
HEARING IN BOTH ZEBRAFISH AND IN
HUMANS.
AND WHY IS ZEBRAFISH SO USEFUL
FOR HEARING AND BALANCE
RESEARCH, YOU KNOW I TOLD YOU
THE REASON IS THE DENSITY OF
HAIR CELLS IN THE LIVING SYSTEM
AND THIS IS JUST 1 WAY, THERE
ARE MANY OTHER WAYS THAT
RESEARCHERS USE TO STUDY HEARING
AND BALANCE, THIS IS 1 OF THEM
BUT THERE ARE A TON OF OTHER
REASONS THAT I DON'T HAVE TIME
IT TELL YOU TODAY, BUT THE MAIN
ADVABTAGE IS THAT WE CAN USE
MODERN TOOLS TO REALLY SEE
WHAT'S HAPPENING IN REKNARREDS
TO HEARING IN THE LIVING ANIMAL.
I WOULD LIKE TO END BY THANKING
PEOPLE WHO HELP ME WITH MY TALK.
SO OLIVIA, HELPED ME MAKE IMAGES
FOR MY SLIDES AND SHE'S SUPER
FUN AND HELPFUL AND ALSO I WOULD
LIKE TO THANK SAMAN HUSSEIN FOR
ALL THOSE VIDEOS AND I WOULD
LIKE TO THANK MY FUNDING FROM
NIDCD, AND EVERYONE FOR
ORGANIZING SUCH A WONDERFUL
SERIES AND THANK YOU GUYS IF -
-FOR YOUR ATTENTION.
>> SO IF PEOPLE WANT TO ASK
KATIE QUESTIONS, PLEASE COME TO
THE MIC AND WE CAN FORM A LINE
AND WHILE YOU GUYS ARE FORMING A
LONG LINE TO ASK HER ALL YOUR
AMAZING QUESTIONS, I WILL START
WITH THE FIRST 1.
I HAVE ACTUALLY 2 QUESTIONS.
ONE IS DO ZEBRAFISH USE VISUAL
CUES?
SO IF YOU WERE TO LIKE PASTE
PEBBLES ON THE BOTTOM OF THEIR
TANK IN SPACE WOULD THEY BE ABLE
TO ORIENT THEMSELVES BASED ON
VISUAL CUES?
>> YOU KNOW THAT'S A GREAT
QUESTION, ACTUALLY.
I DON'T THINK THAT THEY WOULD
WHEREAS HUMANS ARE ABLE TO USE
VISUAL CUES MORE BUT ZEB RAW
DATA FISH HAVE A HARDER TIME
BECAUSE THEY NEED TO SENSE
GRAVITY EMPLOY I THINK IT WOULD
DEPENDOT CUES YOU GAVE THEM BUT
I THINK THEY WOULD BE
DISORIENTED BECAUSE THEY RELY ON
THEIR EARS SO MUCH, BUT THEY DO
SEE AND CAN YOU PLAY THEM VISUAL
CUES IF OTHER CONTEXTS FOR SURE.
AND THEN MY SECOND QUESTION HAS
TO DO WITH YOU SHOWED HOW THERE
ARE GENES IN THE ZEBRAFISH THAT
ARE CLOSELY RELATED TO HUMANS,
BUT IS IT POSSIBLE TO
GENETICALLY ENGINEER ZEBRAFISH
TO YOU KNOW EITHER PUT IN A
HUMAN HEARING GENE OR JUST DO
DIFFERENT, I GUESS INTRODUCE
MUTATIONS SO IS IT POSSIBLE TO
GENETICALLY ENGINEER THE FISH TO
MODEL OTHER HUMAN GENES
RESPONSIBLE FOR HEARING.
>> YEAH, DEFINITELY.
I MEAN ZEBBIA FISH HAS BEEN A
REALLY VALUABLE MODEL FOR HUMAN
GENETICIST, AND A SIMPLE THING
YOU CAN DO IS MUTATE THE GENE IN
ZEB RAW DATA FISH AND LOOK, YOU
COULD DO IT IN A WEEK OR 2 TO
SEE IF THE FISH OR DEAF OR NOT
TO SORT OF VERIFY THAT IT'S A
HUMAN HEARING GENE AND ALSO
CAUSE HEARING LOSS IN FISH, AND
ALSO IF YOU'RE INTERESTED IN A
PARTICULAR MUTATION, CAN YOU
CREATE THAT CHANGE AND
MODTHEY'LL SPECIFIC MUTATION AS
WELL.
>> SOUNDS LOAMACYIC A POWERFUL
TOOL NYEAH, DEFINITELY.
>> KATIE THAT WAS WONDERFUL,
THANK YOU.
MY QUESTION IS HOW DO YOU
DIFIENTIATE BETWEEN SOUND
DETECTION AND FLUID DISPLACEMENT
SO WHEN YOU DID THE TAPPING OF
THE PEIT, RI DISH, YOU CREATED A
PHYSICAL WAVE AS WELL AS AUDIBLE
SOUND BUT THE DEAF FISH DIDN'T
MOVE SO HOW DO YOU DIFFERENTIATE
THE 2 SINCE IT'SOT SURFACE?
>> SO THE LATERAL LINE--YEAH,
THE LATERAL LINE CAN RESPOND TO
THE ACOUSTIC VIBRATIONAL
STIMULUS, SO CAN YOU GIVE
DIFFERENT SOUND STIMRIEW LIE AND
ISOLATE WHAT THE EAR DOES, BUT
DEFINITELY THE LATERAL LINE IS
CONTRIBUTING TO THAT PARTICULAR
SOUND STIMULUS FOR SURE WHICH IS
COOL.
>> THAT WAS BEAUTIFUL, THANK
YOU.
I ALSO HAVE 2 QUESTIONS, FIRST
IS THINKING ABOUT THE GENETICS
OF HEARING AND WERE THERE GENES
THAT WERE FOUND IN DEAF
ZEBRAFISH THAT WEREN'T KNOWN TO
BE PART OF HEARING IN HUMANS AND
LATER PEOPLE LOOKED AND SAID OH
WAIT.
>> YEAH, DEFINITELY.
SO SOME OF THE GENES WERE
IDENTIFIED IN PARALLEL IN MICE,
AS DEAFNESS GENES AND LINKED TO
HUMAN HEARING LOSS AT THE SAME
TIME AND THEN THERE WERE
SEVERAL, I THINK AT LEAST 3 OR 4
GENES THAT YOU KNOW TOOK MAYBE A
DECADE FOR THEM TO AFTER THE
ACCIDENT DENTIFY HUMAN PATIENTS
WITH HEARING LOSS IN THOSE
GENES, BUT YEAH, DEFINITELY.
>> COOL EMPLOY THE OTHER 1 IS
THINKING ABOUT THE IMAGING, THE
REALLY BEAUTIFUL IMAGES OF
RIBBONS FOR THE PURPOSING SO I'M
WONDERING WHAT IS THE SMALLEST
THING THAT YOU CAN IMAGE?
ARE THERE EVEN TIENIER RIBBON
BITS THAT ARE FLOATING AROUND
TOGETHER?
WHAT ARE THE LIMITS OF THIS
TECHNIQUE?
>> WE'RE AT THE LIMIT OF WHAT WE
CAN RESOLVE AND WE CAN'T EVEN
TELL HOW BIG THOSE BABY RIBBONS
ARE BECAUSE THEY'RE SMALLER THAN
OUR TECHNICAL RESOLUTION LIMIT,
BUT WE CAN STILL LIKE DETECT
THEM, YOU KNOW WE CAN'T SAY HOW
BIG THEY ARE.
BUT YEAH, I THINK DEFINITELY,
RIBBONS THEMSELVES ARE A
INTERESTING BEAST, IT'S PROTEIN
AGGREGATING TOGETHER AND THEN
YOU HAVE TO GET ENOUGH TO SEE IT
FOR SURE, I DON'T KNOW.
[LAUGHTER]
>> HI, I JUST WANTED TO ASK WHAT
ARE THE DIFFERENCES BETWEEN THE
DIFFERENT HAIR CELLS IN THE
SIDELINE AND IN THE INNER EAR?
>> I THINK THERE ARE DIFFERENCES
BECAUSE THEY'RE SPECIALIZED TO
SPENCE LIKE THE FLUID FILL IN
THE WATER VERSUS THE SOUND, SO
THEY HAVE DIFFERENT NUMBER OF
CONNECTIONS, SO THE 1S I WAS
SHOWING YOU ARE THE LATERAL LINE
CONNECTIONS WHERE THEY JUST HAVE
3 CONNECTIONS FOR EXAMPLE, BUT
IN THE EAR THEY MIGHT HAVE 10 OR
12, AND ALSO, I THINK THAT WE'RE
NOW FINDING THAT THERE'S EVEN
LIKE WITHIN THE EAR DIFFERENT
TYPES OF HAIR CELLS AS WELL THAT
DETECT MAYBE DIFFERENT
FREQUENCIES SO DIFFERENT TYPES
OF SOUNDS, BUT DEFINITELY THE
STRUCTURES OF THE HAIRS AND THE
STRUCTURE OF THE CONNECTIONS
THAT THEY MAKE ARE DEFINITELY
DIFFERENT AND ALSO WHERE THIS
CONNECTIONS GO IN THE BRAIN ARE
DIFFERENT BECAUSE IT TELLS THE
FISH LIKE DIFFERENT THINGS, LIKE
YOU'RE SENSING WATER OR SENSING
GRAVITY AND SO ON, LIKE THAT,
DOES THAT MAKE SENSE?
GREAT QUESTION.
>> ANY OTHER QUESTIONS?
>> WELL YOU JUST SET ME UP FOR A
QUESTION THAT MAY NOT BE A GOOD
QUESTION, BUT I KNOW YOU FOCUSED
ON EARLY DEVELOPMENT SO I'M
CURIOUS ABOUT HOW LONG DO
ZEBRAFISH LIVE?
AND IS THERE ANY EVIDENCE THEY
MIGHT HAVE SOMETHING AKIN TO
PRESCRIBING BI CUESIS OR HEARING
LOSS AS THEY GET OLD?
>> YEAH, I DON'T KNOW PEOPLE--I
THINK PEOPLE HAVE ATTEMPTED TO
TRY TO CREATE THE ZEBRAFISH
MODEL TO STUDY SOME KIND OF AGE
RELATED HEARING LOSS BUT I DON'T
KNOW IF THEY'VE BEEN SUCCESSFUL.
THE MAIN REASON IS LIKE
ZEBRAFISH UNLIKE HUMANS THEY
JUST REGENERATE THEIR HAIR
CELLS.
I KNOW I'M VERY JEALOUS OF THEM.
I DIDN'T GET INTO IT BUT PEOPLE
HAVE BEEN USING ZEBRAFISH TO
STUDY THIS.
YOU COULD STUDY THEM WITH SOME
AGE RELATED HEARING LOSS AS
WELL.
NTHANK YOU FOR YOUR
PRESENTATION.
I WAS JUF WONDERING HOW THE HAIR
CELLS IN THE EAR LIKE ONLY
RESPONSIBLE FOR HEARING AND THE
1S ON THE SIDELINE ARE THE
POSITIONAL 1S, OR ARE THERE
POSITIONAL HAIR CELLS WITHIN THE
EAR AS WELL?
>> YEAH, GREAT QUESTION.
I DIDN'T GO INTO ALL THE HAIR
CELLS IN THE EAR BUT THERE ARE
DEFINITELY SOME DIFFERENT--YES,
THERE ARE POSITIONAL 1S SO THEY
CAN SENSE SOUNDS COMING FROM
DEFINITE DIRECTIONS AND SO WE
ALSO HAVE HAIR CELLS IN OUR
SEMICIRCULAR CANAL FOR HEAD
MOVEMENT SO THEY ALSO HAVE THOSE
TO DETECT DIFFERENT INCASULAR
MOTIONS OF THE HEAD AS WELL, SO
THEY CAN ALSO USE THEIR HAIR
CELLS TO SENSE DIFFERENT AUDITOR
EXPE VESTIBULAR CUES IN
DIRECTIONAL WAYS AS WELL, FOR
SURE.
VERY GOOD QUESTION.
>> THANK YOU, EVERYONE N.!
>> CAN WE GIVE DR. KINDT JUST 1
MORE ROUND OF APPLAUSE FOR SUCH
AN INFORMATIVE PRESENTATION.
THANK YOU VERY MUCH AGAIN.
AND THANK TO YOU ALL OF YOU WHO
WERE ABLE TO JOIN US FOR TODAY'S
BEYOND THE LAB, UNDERSTANDING
COMMUNICATION DISORDER SPEAKER
SERIES.
WE HOPE YOU ENJOYED TODAY'S
PRESENTATION AND LEARN MORE
ABOUT HOW HAIR CELLS DEVELOP AND
FUNCTION BY OBSERVING THE
ZEBRAFISH AS A MODEL SYSTEM.
JUST A COUPLE HOUSEKEEPING
NOTES, NIDCD STAFF WILL RECEIVE
AN E-MAIL WITH AN EVALUATION
FORM TO GAIN YOUR FEEDBACK ON
TODAY'S PRESENTATION.
WE ASK THAT YOU PLEASE FILL OUT
THAT FORM TO LET US KNOW WHAT
YOU THOUGHT OF TODAY'S LECTURE
AND HOW WE CAN CONTINUE TO BUILD
ON AND IMPROVE FOR FUTURE
LECTURES.
AND LAST BUT NOT LEAST OUR NEXT
BEYOND THE LAB TALK WILL BE HELD
NEXT YEAR AND WE WILL BE SENDING
OUT MORE INFORMATION AS WE GET
CLOSER TO THAT TIME AND AS
SCHEDULES ARE FINALIZED SO
PLEASE BE ON THE LOOK OUT FOR
MORE INFORMATION ABOUT THAT AND
AGAIN JUST WANT TO THANK ALL OF
YOU FOR ATTENDING TODAY AND THAT
WILL CONCLUDE TODAY'S TALK.
THANK YOU VERY MUCH AGAIN.