[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:09.00,0:00:11.00,Default,,0000,0000,0000,,Complexity.
Dialogue: 0,0:00:11.00,0:00:15.00,Default,,0000,0000,0000,,Nothing quite embodies this word\Nlike the human brain.
Dialogue: 0,0:00:15.00,0:00:19.00,Default,,0000,0000,0000,,So for centuries we've studied\Nthe complexity of the human brain
Dialogue: 0,0:00:19.00,0:00:22.00,Default,,0000,0000,0000,,using the tools\Nand technology of the day.
Dialogue: 0,0:00:22.00,0:00:26.00,Default,,0000,0000,0000,,If that's pen and paper\Nfrom the age of da Vinci
Dialogue: 0,0:00:26.00,0:00:29.00,Default,,0000,0000,0000,,through advents in microscopy
Dialogue: 0,0:00:29.00,0:00:32.00,Default,,0000,0000,0000,,to be able to look more deeply\Ninto the brain
Dialogue: 0,0:00:32.00,0:00:36.00,Default,,0000,0000,0000,,to a lot of the new technologies\Nthat you've heard about today
Dialogue: 0,0:00:36.00,0:00:38.00,Default,,0000,0000,0000,,through imaging,\Nmagnetic resonance imaging,
Dialogue: 0,0:00:38.00,0:00:41.00,Default,,0000,0000,0000,,able to look at the details\Nof the brain.
Dialogue: 0,0:00:41.00,0:00:44.00,Default,,0000,0000,0000,,Now one of the first things\Nyou notice when you look
Dialogue: 0,0:00:44.00,0:00:48.00,Default,,0000,0000,0000,,at a fresh human brain\Nis the amount of vasculatur
Dialogue: 0,0:00:48.00,0:00:51.00,Default,,0000,0000,0000,,that's completely covering this.
Dialogue: 0,0:00:51.00,0:00:56.00,Default,,0000,0000,0000,,The brain is this metabolically\Nvoracious organ.
Dialogue: 0,0:00:56.00,0:01:01.00,Default,,0000,0000,0000,,Approximately a quarter of the oxygen\Nin your blood,
Dialogue: 0,0:01:01.00,0:01:04.00,Default,,0000,0000,0000,,approximately a fifth of the glucose\Nin your blood
Dialogue: 0,0:01:04.00,0:01:06.00,Default,,0000,0000,0000,,is being used by this organ.
Dialogue: 0,0:01:06.00,0:01:09.00,Default,,0000,0000,0000,,It's so metabolically active\Nthere's a waste stream
Dialogue: 0,0:01:09.00,0:01:13.00,Default,,0000,0000,0000,,which comes out\Ninto your cervical spinal fluid.
Dialogue: 0,0:01:13.00,0:01:17.00,Default,,0000,0000,0000,,You generate 0.5 liter\Nof CSF every day.
Dialogue: 0,0:01:17.00,0:01:21.00,Default,,0000,0000,0000,,So, as you know, researchers\Nhave taken advantage
Dialogue: 0,0:01:21.00,0:01:25.00,Default,,0000,0000,0000,,of this massive amount of blood flow\Nand metabolic activity
Dialogue: 0,0:01:25.00,0:01:29.00,Default,,0000,0000,0000,,to begin to map regions of the brain,\Nto functionally annotate the brain
Dialogue: 0,0:01:29.00,0:01:31.00,Default,,0000,0000,0000,,in very meaningful ways.
Dialogue: 0,0:01:31.00,0:01:33.00,Default,,0000,0000,0000,,You'll hear a lot more\Nabout those kinds of studies,
Dialogue: 0,0:01:33.00,0:01:38.00,Default,,0000,0000,0000,,but basically taking advantage of the fact\Nthat there's active metabolism
Dialogue: 0,0:01:38.00,0:01:40.00,Default,,0000,0000,0000,,with certain tasks going on.
Dialogue: 0,0:01:40.00,0:01:42.00,Default,,0000,0000,0000,,You can put a living human\Nin a machine
Dialogue: 0,0:01:42.00,0:01:44.00,Default,,0000,0000,0000,,and you can see various areas\Nthat are lighting up.
Dialogue: 0,0:01:44.00,0:01:48.00,Default,,0000,0000,0000,,For example, going around right now\Nis the temporal cortex
Dialogue: 0,0:01:48.00,0:01:51.00,Default,,0000,0000,0000,,auditory processing going on there,\Nyou're listening to my words,
Dialogue: 0,0:01:51.00,0:01:53.00,Default,,0000,0000,0000,,you're processing what I'm saying.
Dialogue: 0,0:01:53.00,0:01:56.00,Default,,0000,0000,0000,,Moving to the front of this brain\Nis your prefontal cortex,
Dialogue: 0,0:01:56.00,0:01:58.00,Default,,0000,0000,0000,,your executive decision-making,
Dialogue: 0,0:01:58.00,0:02:02.00,Default,,0000,0000,0000,,your higher-thinking areas\Nof the brain.
Dialogue: 0,0:02:02.00,0:02:08.00,Default,,0000,0000,0000,,And so the thing that\Nwe're very much interested in
Dialogue: 0,0:02:08.00,0:02:10.00,Default,,0000,0000,0000,,from the perspective\Nof the Allen Institute
Dialogue: 0,0:02:10.00,0:02:13.00,Default,,0000,0000,0000,,is to go deeper,\Nto get down to the cellular level.
Dialogue: 0,0:02:13.00,0:02:17.00,Default,,0000,0000,0000,,So when you look at this slice, it doesn't\Nreally look like gray matter, does it?
Dialogue: 0,0:02:17.00,0:02:20.00,Default,,0000,0000,0000,,It's more tan matter, or beige matter.
Dialogue: 0,0:02:20.00,0:02:25.00,Default,,0000,0000,0000,,And scientists about, I guess\Naround the late 1800's,
Dialogue: 0,0:02:25.00,0:02:28.00,Default,,0000,0000,0000,,discovered that they could stain tissue\Nin various ways,
Dialogue: 0,0:02:28.00,0:02:33.00,Default,,0000,0000,0000,,and this sort of came along\Nwith various microscopy techniques.
Dialogue: 0,0:02:33.00,0:02:37.00,Default,,0000,0000,0000,,And so this is a stain, it's called Nissl,\Nand it stains cell bodies,
Dialogue: 0,0:02:37.00,0:02:40.00,Default,,0000,0000,0000,,it stains the cell bodies purple.
Dialogue: 0,0:02:40.00,0:02:43.00,Default,,0000,0000,0000,,And so you can see\Na lot more structure and texture
Dialogue: 0,0:02:43.00,0:02:45.00,Default,,0000,0000,0000,,when you look at something like this.
Dialogue: 0,0:02:45.00,0:02:49.00,Default,,0000,0000,0000,,You can see the outer layers of the brain\Nand the neocortex,
Dialogue: 0,0:02:49.00,0:02:54.00,Default,,0000,0000,0000,,there's a six-layer structure, arguably\Nwhat makes us most uniquely human.
Dialogue: 0,0:02:54.00,0:02:58.00,Default,,0000,0000,0000,,As you've heard before about\Nthere's on average in a human,
Dialogue: 0,0:02:58.00,0:03:03.00,Default,,0000,0000,0000,,there's about 86 billion neurons,\Nand those 86 billion neurons
Dialogue: 0,0:03:03.00,0:03:05.00,Default,,0000,0000,0000,,you can see are not evenly distributed,
Dialogue: 0,0:03:05.00,0:03:09.00,Default,,0000,0000,0000,,they're very focused\Nand specific structures.
Dialogue: 0,0:03:09.00,0:03:11.00,Default,,0000,0000,0000,,And each of them\Nhas their own sort of function
Dialogue: 0,0:03:11.00,0:03:15.00,Default,,0000,0000,0000,,both on an anatomic level\Nand at a cellular level.
Dialogue: 0,0:03:15.00,0:03:19.00,Default,,0000,0000,0000,,So if we zoom in on these cells,\Nwhat you can see is large cells
Dialogue: 0,0:03:19.00,0:03:23.00,Default,,0000,0000,0000,,and small support cells\Nthat are glias and astrocytes
Dialogue: 0,0:03:23.00,0:03:27.00,Default,,0000,0000,0000,,and these cells are as we know\Nconnected in a variety of different ways.
Dialogue: 0,0:03:27.00,0:03:31.00,Default,,0000,0000,0000,,And we like to think about,\Nalthough there's 86 billion cells,
Dialogue: 0,0:03:31.00,0:03:36.00,Default,,0000,0000,0000,,each cell might be considered a snowflake,\Nthey're actually able to be binned
Dialogue: 0,0:03:36.00,0:03:39.00,Default,,0000,0000,0000,,into a large number\Nof cell types or classes.
Dialogue: 0,0:03:39.00,0:03:43.00,Default,,0000,0000,0000,,What flavor of activity\Nthat particular cell class has
Dialogue: 0,0:03:43.00,0:03:49.00,Default,,0000,0000,0000,,is driven by the underlying genes\Nthat are turned on in that cell,
Dialogue: 0,0:03:49.00,0:03:53.00,Default,,0000,0000,0000,,those drive protein expression\Nwhich guide the function of those cells,
Dialogue: 0,0:03:53.00,0:03:56.00,Default,,0000,0000,0000,,who they're connected to,\Nwhat their morphology is,
Dialogue: 0,0:03:56.00,0:04:00.00,Default,,0000,0000,0000,,and we're very much interested\Nin understanding these cell classes.
Dialogue: 0,0:04:00.00,0:04:02.00,Default,,0000,0000,0000,,So how do we do that?
Dialogue: 0,0:04:02.00,0:04:05.00,Default,,0000,0000,0000,,Well, we look inside the cell\Nat the nucleus,
Dialogue: 0,0:04:05.00,0:04:07.00,Default,,0000,0000,0000,,(and it will get to the nucleus)
Dialogue: 0,0:04:07.00,0:04:10.00,Default,,0000,0000,0000,,and so inside we've got\N23 pairs of chromosomes,
Dialogue: 0,0:04:10.00,0:04:12.00,Default,,0000,0000,0000,,we've got a pair from mom,\Na pair from dad,
Dialogue: 0,0:04:12.00,0:04:17.00,Default,,0000,0000,0000,,on those chromosomes about 25000 genes\Nand we're very much again interested in
Dialogue: 0,0:04:17.00,0:04:22.00,Default,,0000,0000,0000,,understanding which of these 25000 genes\Nare turned on
Dialogue: 0,0:04:22.00,0:04:24.00,Default,,0000,0000,0000,,at what levels they're turned on.
Dialogue: 0,0:04:24.00,0:04:28.00,Default,,0000,0000,0000,,Those are going to, of course, drive\Nthe underlying biochemistry of the cells
Dialogue: 0,0:04:28.00,0:04:33.00,Default,,0000,0000,0000,,they're turned on in and again every cell\Nin our bodies more or less has these
Dialogue: 0,0:04:33.00,0:04:35.00,Default,,0000,0000,0000,,and we want to understand better
Dialogue: 0,0:04:35.00,0:04:41.00,Default,,0000,0000,0000,,what the driving biochemistry\Ndriven by our genome is.
Dialogue: 0,0:04:41.00,0:04:44.00,Default,,0000,0000,0000,,So how do we do that?
Dialogue: 0,0:04:47.00,0:04:51.00,Default,,0000,0000,0000,,We're going to deconstruct a brain\Nin several easy steps.
Dialogue: 0,0:04:51.00,0:04:54.00,Default,,0000,0000,0000,,So we start\Nat a medical examiner's office.
Dialogue: 0,0:04:54.00,0:04:56.00,Default,,0000,0000,0000,,This is a place\Nwhere the dead are brought in
Dialogue: 0,0:04:56.00,0:04:58.00,Default,,0000,0000,0000,,and obviously it's useful
Dialogue: 0,0:04:58.00,0:05:03.00,Default,,0000,0000,0000,,for the kind of work we do,\N[it] is not non-invasive,
Dialogue: 0,0:05:03.00,0:05:08.00,Default,,0000,0000,0000,,we actually need\Nto obtain fresh brain tissue
Dialogue: 0,0:05:08.00,0:05:13.00,Default,,0000,0000,0000,,and we need to obtain it within 24 hours\Nbecause the tissues start to degrade.
Dialogue: 0,0:05:13.00,0:05:15.00,Default,,0000,0000,0000,,We also wanted for our projects\Nto have normal tissue
Dialogue: 0,0:05:15.00,0:05:18.00,Default,,0000,0000,0000,,as much normal as we could possibly get.
Dialogue: 0,0:05:18.00,0:05:24.00,Default,,0000,0000,0000,,So over the course of a two-\Nor three-year collection time window
Dialogue: 0,0:05:24.00,0:05:30.00,Default,,0000,0000,0000,,we collected 6 very high-quality brains,\N5 of them were male, one was female.
Dialogue: 0,0:05:30.00,0:05:35.00,Default,,0000,0000,0000,,That's only because males\Ntend to die untimely deaths
Dialogue: 0,0:05:35.00,0:05:39.00,Default,,0000,0000,0000,,more frequently than females,\Nand then to add to that,
Dialogue: 0,0:05:39.00,0:05:42.00,Default,,0000,0000,0000,,females are much more likely\Nto give consent
Dialogue: 0,0:05:42.00,0:05:45.00,Default,,0000,0000,0000,,for us to take the brain\Nthan vice versa.
Dialogue: 0,0:05:45.00,0:05:49.00,Default,,0000,0000,0000,,We have to figure that one out.
Dialogue: 0,0:05:49.00,0:05:52.00,Default,,0000,0000,0000,,We've heard people say,\N“He wasn't using it anyway!”
Dialogue: 0,0:05:52.00,0:05:55.00,Default,,0000,0000,0000,,(Laughter)
Dialogue: 0,0:05:56.00,0:06:00.00,Default,,0000,0000,0000,,So, once the brain comes in\Nwe have to move very, very quickly.
Dialogue: 0,0:06:00.00,0:06:06.00,Default,,0000,0000,0000,,So first we capture\Na magnetic resonance image.
Dialogue: 0,0:06:06.00,0:06:08.00,Default,,0000,0000,0000,,This, of course,\Nwill look very familiar to you,
Dialogue: 0,0:06:08.00,0:06:11.00,Default,,0000,0000,0000,,but this is going to be the structure\Nin which we hang all of this information,
Dialogue: 0,0:06:11.00,0:06:15.00,Default,,0000,0000,0000,,it's also a common coordinate framework\Nby which the many, many researchers
Dialogue: 0,0:06:15.00,0:06:17.00,Default,,0000,0000,0000,,who do imaging studies can map
Dialogue: 0,0:06:17.00,0:06:20.00,Default,,0000,0000,0000,,into our ultimate database,\Nan Atlas framework.
Dialogue: 0,0:06:20.00,0:06:22.00,Default,,0000,0000,0000,,We also collect diffusion tensor images
Dialogue: 0,0:06:22.00,0:06:25.00,Default,,0000,0000,0000,,so we get some of the wiring\Nfrom these brains.
Dialogue: 0,0:06:25.00,0:06:29.00,Default,,0000,0000,0000,,And then the brain is removed\Nfrom the skull. It's slabbed and frozen,
Dialogue: 0,0:06:29.00,0:06:32.00,Default,,0000,0000,0000,,frozen solid,\Nand then it's shipped to Seattle
Dialogue: 0,0:06:32.00,0:06:34.00,Default,,0000,0000,0000,,where we have\Nthe Allen Institute for Brain Science.
Dialogue: 0,0:06:34.00,0:06:36.00,Default,,0000,0000,0000,,We have great technicians\Nwho've worked out
Dialogue: 0,0:06:36.00,0:06:39.00,Default,,0000,0000,0000,,a lot of great techniques\Nfor further processing.
Dialogue: 0,0:06:39.00,0:06:45.00,Default,,0000,0000,0000,,So first, we take a very thin section,\Nthis is 25µm thin section,
Dialogue: 0,0:06:45.00,0:06:48.00,Default,,0000,0000,0000,,which is about a baby's hair width.
Dialogue: 0,0:06:48.00,0:06:52.00,Default,,0000,0000,0000,,That's transferred to a microscope slide\Nand then that is stained
Dialogue: 0,0:06:52.00,0:06:55.00,Default,,0000,0000,0000,,with one of those histological stains\Nthat I talked about before.
Dialogue: 0,0:06:55.00,0:06:58.00,Default,,0000,0000,0000,,And this is going to give us more contrast\Nas our team of anatomists
Dialogue: 0,0:06:58.00,0:07:02.00,Default,,0000,0000,0000,,start to make assignments of anatomy.
Dialogue: 0,0:07:05.00,0:07:06.00,Default,,0000,0000,0000,,So we digitize these images,
Dialogue: 0,0:07:06.00,0:07:11.00,Default,,0000,0000,0000,,everything goes from being wet lab\Nto being dry lab.
Dialogue: 0,0:07:11.00,0:07:15.00,Default,,0000,0000,0000,,And then combined with anatomy\Nthat we get from the MR,
Dialogue: 0,0:07:15.00,0:07:17.00,Default,,0000,0000,0000,,we further fragment the brain.
Dialogue: 0,0:07:17.00,0:07:24.00,Default,,0000,0000,0000,,This is to get it into a smaller framework\Nfor which we can do this.
Dialogue: 0,0:07:24.00,0:07:27.00,Default,,0000,0000,0000,,So here's a technician\Nwho's doing additional cutting.
Dialogue: 0,0:07:27.00,0:07:30.00,Default,,0000,0000,0000,,This is again a 25µm thin section.
Dialogue: 0,0:07:30.00,0:07:32.00,Default,,0000,0000,0000,,You'll see da Vinci's tools,\Nthe paintbrush,
Dialogue: 0,0:07:32.00,0:07:34.00,Default,,0000,0000,0000,,being use here to smooth this out.
Dialogue: 0,0:07:34.00,0:07:37.00,Default,,0000,0000,0000,,This is fresh frozen brain tissue.
Dialogue: 0,0:07:39.00,0:07:42.00,Default,,0000,0000,0000,,And it can be very carefully\Nmelted to a microscope slide.
Dialogue: 0,0:07:42.00,0:07:44.00,Default,,0000,0000,0000,,You'll note\Nthat there's a barcode on the slide.
Dialogue: 0,0:07:44.00,0:07:46.00,Default,,0000,0000,0000,,We process 1000's and 1000's of samples,
Dialogue: 0,0:07:46.00,0:07:50.00,Default,,0000,0000,0000,,we track all of it in a backend\Ninformation management system.
Dialogue: 0,0:07:50.00,0:07:53.00,Default,,0000,0000,0000,,Those are stained.
Dialogue: 0,0:07:53.00,0:07:57.00,Default,,0000,0000,0000,,And then we get\Nmore detailed anatomic information.
Dialogue: 0,0:07:57.00,0:08:08.00,Default,,0000,0000,0000,,That information is ... (playing here)\N... this is a laser capture microscope,
Dialogue: 0,0:08:08.00,0:08:12.00,Default,,0000,0000,0000,,the lab technician is actually describing\Nan area on that slide.
Dialogue: 0,0:08:12.00,0:08:15.00,Default,,0000,0000,0000,,And a laser, you see the blue light\Ncutting around there,
Dialogue: 0,0:08:15.00,0:08:17.00,Default,,0000,0000,0000,,very James Bond like.
Dialogue: 0,0:08:17.00,0:08:20.00,Default,,0000,0000,0000,,Cutting out part of that,\Nand underneath there,
Dialogue: 0,0:08:20.00,0:08:23.00,Default,,0000,0000,0000,,you can see the blue light again,\Nfrom the microscope in real-time,
Dialogue: 0,0:08:23.00,0:08:28.00,Default,,0000,0000,0000,,it's collecting in a microscope tube\Nthat tissue.
Dialogue: 0,0:08:28.00,0:08:30.00,Default,,0000,0000,0000,,We extract RNA,
Dialogue: 0,0:08:30.00,0:08:35.00,Default,,0000,0000,0000,,RNA is the product of the genes\Nthat are being turned on,
Dialogue: 0,0:08:35.00,0:08:38.00,Default,,0000,0000,0000,,and we label it,\Nwe put a fluorescent tag on it.
Dialogue: 0,0:08:38.00,0:08:39.00,Default,,0000,0000,0000,,Now what you are looking at here
Dialogue: 0,0:08:39.00,0:08:43.00,Default,,0000,0000,0000,,is a constellation\Nof the entire human genome
Dialogue: 0,0:08:43.00,0:08:45.00,Default,,0000,0000,0000,,spread out over a glass slide.
Dialogue: 0,0:08:45.00,0:08:48.00,Default,,0000,0000,0000,,Those little bits are representing\Nthe 25000 genes.
Dialogue: 0,0:08:48.00,0:08:52.00,Default,,0000,0000,0000,,There's about 60000 of these spots\Nand that fluorescently labeled RNA
Dialogue: 0,0:08:52.00,0:08:56.00,Default,,0000,0000,0000,,is put onto this microscope slide\Nand then we read out quantitatively
Dialogue: 0,0:08:56.00,0:09:00.00,Default,,0000,0000,0000,,what genes are turned on at what levels.
Dialogue: 0,0:09:00.00,0:09:04.00,Default,,0000,0000,0000,,So we do this over and over and over again\Nfor brains that we've collected;
Dialogue: 0,0:09:04.00,0:09:07.00,Default,,0000,0000,0000,,as I mentioned we've collected\N6 brains in total.
Dialogue: 0,0:09:07.00,0:09:10.00,Default,,0000,0000,0000,,We collect samples\Nfrom about 1000 structures in every brain
Dialogue: 0,0:09:10.00,0:09:14.00,Default,,0000,0000,0000,,that we've looked at,\Nso it's a massive amount of data.
Dialogue: 0,0:09:14.00,0:09:18.00,Default,,0000,0000,0000,,And we pull all of this together,\Nback into a common framework,
Dialogue: 0,0:09:18.00,0:09:22.00,Default,,0000,0000,0000,,that is a free and open resource\Nfor scientists around the world to use.
Dialogue: 0,0:09:22.00,0:09:24.00,Default,,0000,0000,0000,,So at the Allen Institute\Nfor Brain Science,
Dialogue: 0,0:09:24.00,0:09:28.00,Default,,0000,0000,0000,,we've been generating these kinds\Nof data resources for almost a decade.
Dialogue: 0,0:09:28.00,0:09:32.00,Default,,0000,0000,0000,,They're free to use for anybody,\Nthey're online tools,
Dialogue: 0,0:09:32.00,0:09:38.00,Default,,0000,0000,0000,,just for example today a given workday,\Nthere'll be about 1000 unique visitors
Dialogue: 0,0:09:38.00,0:09:43.00,Default,,0000,0000,0000,,that come in from labs around the world\Nto come use our resources and data.
Dialogue: 0,0:09:43.00,0:09:47.00,Default,,0000,0000,0000,,They get access to tools like this,\Nwhich allows them to see
Dialogue: 0,0:09:47.00,0:09:50.00,Default,,0000,0000,0000,,all of that anatomy and the structure\Nthat we created before
Dialogue: 0,0:09:50.00,0:09:55.00,Default,,0000,0000,0000,,and to start mapping in then the things\Nthat they're particularly interested in.
Dialogue: 0,0:09:55.00,0:09:57.00,Default,,0000,0000,0000,,So in this case you're looking\Nat the structure
Dialogue: 0,0:09:57.00,0:09:59.00,Default,,0000,0000,0000,,and they're going to look\Nat these color balls
Dialogue: 0,0:09:59.00,0:10:02.00,Default,,0000,0000,0000,,are representing a particular gene\Nthey're interested in
Dialogue: 0,0:10:02.00,0:10:05.00,Default,,0000,0000,0000,,that's either being turned up or down
Dialogue: 0,0:10:05.00,0:10:11.00,Default,,0000,0000,0000,,in those various areas depending upon\Nthe heat color that's specified there.
Dialogue: 0,0:10:11.00,0:10:14.00,Default,,0000,0000,0000,,So what are people doing when they come in\Nand using these resources?
Dialogue: 0,0:10:14.00,0:10:17.00,Default,,0000,0000,0000,,Well, one of the things\Nthat you might hear lots about
Dialogue: 0,0:10:17.00,0:10:19.00,Default,,0000,0000,0000,,is human genetic studies.
Dialogue: 0,0:10:19.00,0:10:23.00,Default,,0000,0000,0000,,Obviously if you're very interested\Nin understanding disease
Dialogue: 0,0:10:23.00,0:10:25.00,Default,,0000,0000,0000,,there's a genetic underpinning\Nto many of them.
Dialogue: 0,0:10:25.00,0:10:28.00,Default,,0000,0000,0000,,So you'd like more information,\Nyou do a large-scale study
Dialogue: 0,0:10:28.00,0:10:31.00,Default,,0000,0000,0000,,and you get out of those studies\Ncollections of genes
Dialogue: 0,0:10:31.00,0:10:34.00,Default,,0000,0000,0000,,and one of the first things you're going\Nto want to know is more information.
Dialogue: 0,0:10:34.00,0:10:41.00,Default,,0000,0000,0000,,Is there something I can learn\Nabout the location of these genes
Dialogue: 0,0:10:41.00,0:10:44.00,Default,,0000,0000,0000,,that gives me additional clues\Nas to their function,
Dialogue: 0,0:10:44.00,0:10:49.00,Default,,0000,0000,0000,,ways in which I might intervene\Nin the disease process.
Dialogue: 0,0:10:49.00,0:10:52.00,Default,,0000,0000,0000,,They're also very interested\Nin understanding human genetic diversity.
Dialogue: 0,0:10:52.00,0:10:59.00,Default,,0000,0000,0000,,Now we've already looked at 6 brains but\Nas we know, every human is very unique.
Dialogue: 0,0:10:59.00,0:11:01.00,Default,,0000,0000,0000,,We celebrate our differences;
Dialogue: 0,0:11:01.00,0:11:05.00,Default,,0000,0000,0000,,this is a snapshot of the great workforce\Nat the Allen Institute for Brain Science
Dialogue: 0,0:11:05.00,0:11:09.00,Default,,0000,0000,0000,,who does all the great work\Nthat I'm talking about today.
Dialogue: 0,0:11:09.00,0:11:15.00,Default,,0000,0000,0000,,But remarkably when we look at this level\Nat the underlying data,
Dialogue: 0,0:11:15.00,0:11:20.00,Default,,0000,0000,0000,,and this is a lot of data from\N2 completely unrelated individuals,
Dialogue: 0,0:11:20.00,0:11:24.00,Default,,0000,0000,0000,,there's a very high degree\Nof correlation, correspondence.
Dialogue: 0,0:11:24.00,0:11:26.00,Default,,0000,0000,0000,,So this is looking at 1000's\Nof different measurements
Dialogue: 0,0:11:26.00,0:11:30.00,Default,,0000,0000,0000,,of gene expression across\Nmany, many different areas of the brain;
Dialogue: 0,0:11:30.00,0:11:32.00,Default,,0000,0000,0000,,and there's\Na very high degree of correspondence.
Dialogue: 0,0:11:32.00,0:11:33.00,Default,,0000,0000,0000,,This was very reassuring to us.
Dialogue: 0,0:11:33.00,0:11:36.00,Default,,0000,0000,0000,,First because when you generate data\Non this scale
Dialogue: 0,0:11:36.00,0:11:38.00,Default,,0000,0000,0000,,you want to make sure\Nthat it's high quality,
Dialogue: 0,0:11:38.00,0:11:41.00,Default,,0000,0000,0000,,so reproducibility is obviously important,
Dialogue: 0,0:11:41.00,0:11:43.00,Default,,0000,0000,0000,,but it was also important\Nbecause we feel that it's given us
Dialogue: 0,0:11:43.00,0:11:46.00,Default,,0000,0000,0000,,a great snapshot into the human brain.
Dialogue: 0,0:11:46.00,0:11:50.00,Default,,0000,0000,0000,,And the people using the data,\Neven with our low n, have confidence
Dialogue: 0,0:11:50.00,0:11:53.00,Default,,0000,0000,0000,,that what they're seeing\Nhas some relevance.
Dialogue: 0,0:11:53.00,0:11:58.00,Default,,0000,0000,0000,,Now, not everything is correlated here,\Nyou can see some outliers,
Dialogue: 0,0:11:58.00,0:12:00.00,Default,,0000,0000,0000,,and, of course, those outliers\Nare going to be interesting
Dialogue: 0,0:12:00.00,0:12:03.00,Default,,0000,0000,0000,,related to human differences.
Dialogue: 0,0:12:03.00,0:12:04.00,Default,,0000,0000,0000,,We did study a couple of years ago
Dialogue: 0,0:12:04.00,0:12:09.00,Default,,0000,0000,0000,,in which we tried to understand\Na little better about those differences
Dialogue: 0,0:12:09.00,0:12:12.00,Default,,0000,0000,0000,,and looked at multiple individuals\Nand different gene products
Dialogue: 0,0:12:12.00,0:12:15.00,Default,,0000,0000,0000,,and what we find as a tendency\Nand as a rule
Dialogue: 0,0:12:15.00,0:12:19.00,Default,,0000,0000,0000,,is that those differences tend to be\Nin very specific cell populations
Dialogue: 0,0:12:19.00,0:12:23.00,Default,,0000,0000,0000,,or cell types, cell classes,\Nas I mentioned before.
Dialogue: 0,0:12:23.00,0:12:27.00,Default,,0000,0000,0000,,So, this is an example\Nof 2 different genes that are turned on
Dialogue: 0,0:12:27.00,0:12:29.00,Default,,0000,0000,0000,,in very specific layers\Nof the neocortex
Dialogue: 0,0:12:29.00,0:12:32.00,Default,,0000,0000,0000,,only in one individual\Nand not found in another.
Dialogue: 0,0:12:32.00,0:12:36.00,Default,,0000,0000,0000,,Now we have no idea\Nif that's due to environmental changes,
Dialogue: 0,0:12:36.00,0:12:39.00,Default,,0000,0000,0000,,environmental influences\Nor if it's just genetics,
Dialogue: 0,0:12:39.00,0:12:43.00,Default,,0000,0000,0000,,but we did do a study in which we looked\Nat the mouse several years ago
Dialogue: 0,0:12:43.00,0:12:48.00,Default,,0000,0000,0000,,and we were looking at genes\Nthat encode for, in this case a DRD2,
Dialogue: 0,0:12:48.00,0:12:52.00,Default,,0000,0000,0000,,the gene listed on the top\Nis a dopamine receptor.
Dialogue: 0,0:12:52.00,0:12:58.00,Default,,0000,0000,0000,,Tyrosine hydroxylase (TH) is\Na gene involved in dopamine biosynthesis
Dialogue: 0,0:12:58.00,0:13:03.00,Default,,0000,0000,0000,,and those 2 gene products\Nare very different in the cell types
Dialogue: 0,0:13:03.00,0:13:06.00,Default,,0000,0000,0000,,in these individual mouse brains.
Dialogue: 0,0:13:06.00,0:13:11.00,Default,,0000,0000,0000,,So, over on the left is “C57 black 6”\Nwhich is a commonly used mouse strain,
Dialogue: 0,0:13:11.00,0:13:15.00,Default,,0000,0000,0000,,and then spread at the other end\Nis a wild type strain.
Dialogue: 0,0:13:15.00,0:13:19.00,Default,,0000,0000,0000,,And so the further you go\Nthe more genetically unrelated you are.
Dialogue: 0,0:13:19.00,0:13:23.00,Default,,0000,0000,0000,,And when we looked in total across,\Nsort of evolution if you will,
Dialogue: 0,0:13:23.00,0:13:25.00,Default,,0000,0000,0000,,across genetic relatedness,
Dialogue: 0,0:13:25.00,0:13:28.00,Default,,0000,0000,0000,,the further you were\Ngenetically unrelated,
Dialogue: 0,0:13:28.00,0:13:30.00,Default,,0000,0000,0000,,the more of\Nthese very specific cell types,
Dialogue: 0,0:13:30.00,0:13:34.00,Default,,0000,0000,0000,,specific changes, you could see.
Dialogue: 0,0:13:34.00,0:13:36.00,Default,,0000,0000,0000,,So at the Allen Institute\Nfor the next decade
Dialogue: 0,0:13:36.00,0:13:38.00,Default,,0000,0000,0000,,we're embarking\Non a pretty ambitious program
Dialogue: 0,0:13:38.00,0:13:43.00,Default,,0000,0000,0000,,to start to understand the cell types,\Nunderstand the cell differences
Dialogue: 0,0:13:43.00,0:13:46.00,Default,,0000,0000,0000,,and how they ultimately relate\Nto the functional properties of the brain.
Dialogue: 0,0:13:46.00,0:13:50.00,Default,,0000,0000,0000,,This is, I think, critical information\Nfor the entire field,
Dialogue: 0,0:13:50.00,0:13:54.00,Default,,0000,0000,0000,,to start linking up all\Nof these fundamental parts
Dialogue: 0,0:13:54.00,0:13:57.00,Default,,0000,0000,0000,,which are the cells,\Nto how they're connected,
Dialogue: 0,0:13:57.00,0:14:00.00,Default,,0000,0000,0000,,the underlying molecules\Nthat drive those connections,
Dialogue: 0,0:14:00.00,0:14:04.00,Default,,0000,0000,0000,,the underlying molecules\Nthat drive the physiological properties,
Dialogue: 0,0:14:04.00,0:14:06.00,Default,,0000,0000,0000,,the electric chemical properties
Dialogue: 0,0:14:06.00,0:14:09.00,Default,,0000,0000,0000,,and then ultimately\Nthe functional properties of those cells.
Dialogue: 0,0:14:09.00,0:14:14.00,Default,,0000,0000,0000,,So we're doing this\Nin 3 different areas of research.
Dialogue: 0,0:14:14.00,0:14:17.00,Default,,0000,0000,0000,,First, we're focusing on the mouse,\Nthe mouse visual system,
Dialogue: 0,0:14:17.00,0:14:21.00,Default,,0000,0000,0000,,to look at, in real-time,\Nin the living animal,
Dialogue: 0,0:14:21.00,0:14:25.00,Default,,0000,0000,0000,,the functions of a variety\Nof different cells.
Dialogue: 0,0:14:25.00,0:14:28.00,Default,,0000,0000,0000,,We're linking these in this concept\Nin the middle of cell types,
Dialogue: 0,0:14:28.00,0:14:33.00,Default,,0000,0000,0000,,trying to really understand\Nthe underlying molecules
Dialogue: 0,0:14:33.00,0:14:37.00,Default,,0000,0000,0000,,in all the properties\Nas they relate to those functions
Dialogue: 0,0:14:37.00,0:14:40.00,Default,,0000,0000,0000,,and then we're looking\Nat the human.
Dialogue: 0,0:14:40.00,0:14:44.00,Default,,0000,0000,0000,,In the human we're doing this both\Nin the middle and cell types
Dialogue: 0,0:14:44.00,0:14:46.00,Default,,0000,0000,0000,,using the tissue driven work\Nthat I talked about before
Dialogue: 0,0:14:46.00,0:14:51.00,Default,,0000,0000,0000,,but also we're doing it in vitro\Nusing stem cell technology.
Dialogue: 0,0:14:51.00,0:14:55.00,Default,,0000,0000,0000,,We're learning how to make\Nvery specific cell types within the dish
Dialogue: 0,0:14:55.00,0:14:58.00,Default,,0000,0000,0000,,and then being able to test\Nthose functional properties
Dialogue: 0,0:14:58.00,0:15:04.00,Default,,0000,0000,0000,,and go back and forth between\Nwhat we learn in the mouse to the human.
Dialogue: 0,0:15:04.00,0:15:08.00,Default,,0000,0000,0000,,So, with that I will finish\Nand just say that it's an exciting time
Dialogue: 0,0:15:08.00,0:15:11.00,Default,,0000,0000,0000,,to be in biology and an exciting time\Nto be in neuroscience.
Dialogue: 0,0:15:11.00,0:15:15.00,Default,,0000,0000,0000,,I think the technology of the day\Nhas come well beyond the pen and paper
Dialogue: 0,0:15:15.00,0:15:20.00,Default,,0000,0000,0000,,and it's really time for a renaissance in\Nour understanding of this complex organ.
Dialogue: 0,0:15:20.00,0:15:21.00,Default,,0000,0000,0000,,Thanks.
Dialogue: 0,0:15:21.00,0:15:27.00,Default,,0000,0000,0000,,(Applause)