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Developmental Biology of a Simple Organism: Bacillus subtilis

Transcript of Part 1: Spore Formation in B. Subtilis

00:00:07.09		Hello, my name is Richard Losick and I'm a professor at Harvard University.
00:00:12.16		The title of my presentation is "Developmental biology of a simple organism."
00:00:17.25		We generally think of biological development in the context of complex multicellular organisms.
00:00:24.27		But, even the most primitive kinds of cells can also exhibit dramatic processes
00:00:30.25		of cellular differentiation and morphogenesis. I'm going to tell you one such example,
00:00:35.20		with the spore forming bacterium Bacillus subtilis.
00:00:39.22		Let me introduce Bacillus subtilis to you in the way it was introduced
00:00:43.17		to the academic community in 1877 by its discoverer Ferdinand Cohn.
00:00:50.29		Ferdinand Cohn published his findings in the Biology of Plants and he drew what he saw
00:00:59.02		in this marvelous plate that you see here. And what's apparent in the plate
00:01:04.22		is that he saw long chains of cells that had tiny ovoid bodies in them
00:01:10.07		which he recognized as bacterial spores. So this marked the discovery
00:01:14.17		of spore formation by a bacterium.
00:01:19.28		You should also know that this benign bacterium Bacillus subtilis has an evil cousin.
00:01:26.26		It’s the anthrax causing pathogen Bacillus anthracis which was discovered
00:01:31.29		by Robert Koch at about the same time as Cohn.  And Cohn and Koch
00:01:37.17		agreed to publish their findings back to back in the Biology of Plants and, in fact, this cartoon
00:01:43.03		of drawings contains contributions of Koch for Bacillus anthracis
00:01:50.04		as well as for Cohn for Bacillus subtilis.
00:01:54.23		I've divided my presentation into three parts. The first part concerns the process,
00:02:02.05		the overall process by which B. subtilis makes a spore.
00:02:07.22		The second part is new research on multicellularity. We traditionally have thought
00:02:13.25		of Bacillus subtilis and many other bacteria as being solitary creatures
00:02:18.07		that go about their business as individual cells, but now we've come to appreciate that
00:02:23.14		Bacillus subtilis makes elaborate multicellular communities and that
00:02:28.01		spore formation takes place in these communities.
00:02:32.09		The last part is the topic of stochasticity and cell fate.
00:02:38.00		It’s generally believed that cell fate decisions
00:02:42.01		in developmental biology are highly determined.
00:02:45.11		And indeed they are. But increasingly we've begun to see examples in which
00:02:51.08		decisions about cell fate are made in a stochastic fashion
00:02:56.27		and that will be the topic of my last presentation
00:02:59.26		which will have four examples from Bacillus subtilis.
00:03:04.27		OK, so to begin this part of my talk:
00:03:09.07		Bacillus subtilis makes a spore. How does it do it?
00:03:12.12		So there are three main topics: The first is that spore formation involves two cells.
00:03:20.11		So this is really a tale of two cells. You'll see that two cells collaborate in making a single spore.
00:03:27.09		Having created two cells, each cell has its own fate,
00:03:31.12		follows its own distinct program of gene expression,
00:03:36.01		and this is governed by a series of transcription factors that act in a cell specific fashion.
00:03:43.02		The final part of my talk concerns how the two cells talk to each other.
00:03:49.11		The two cells are not completely independent, even though they follow
00:03:52.18		their own distinct programs of gene expression, but rather they talk back and forth
00:03:57.05		at each stage of development to keep the two processes in coordination with each other.
00:04:04.10		Here in cartoon form are the principle stages of spore formation.
00:04:09.15		Spore formation is triggered by nutrient limitation and that results in the cells entering a pathway
00:04:16.17		that involves the formation of two different cells. At the very start we have a single cell,
00:04:24.20		and I'll refer to that as the pre-divisional sporangium.
00:04:27.25		Then that pre-divisional sporangium undergoes
00:04:31.00		a conspicuously asymmetric process of cell division in which a division septum is
00:04:37.25		formed near an extreme pole of the cell.  That divides the developing cell into
00:04:43.26		two cells; a forespore cell, the smaller cell, and a larger mother cell.
00:04:49.13		The forespore is destined to become the spore,
00:04:52.18		whereas the mother cell nurtures the developing spore
00:04:56.09		and eventually liberates the mature spore. At this early stage of development,
00:05:02.14		the forespore and the mother cell lie side by side. But later in development,
00:05:07.04		in a remarkable cell biological process, the mother cell swallows up the forespore,
00:05:13.26		in a process that resembles phagocytosis in higher cells,
00:05:18.13		fully engulfing the forespore and pinching
00:05:21.07		it off as a free cell in the mother cell cytoplasm to create a cell within a cell.
00:05:26.22		So that inner cell will become the spore and the outer mother cell nurtures the spore and
00:05:32.24		then eventually will liberate the spore by lysing.
00:05:36.15		Here are fluorescence micrographs of cells at these various stages of sporulation.
00:05:42.25		The cells have been stained with a membrane dye
00:05:45.09		to highlight the features that I've been speaking about.
00:05:47.15		So, at the stage of asymmetric division, you can see that a polar septum is formed
00:05:53.21		at an extreme polar position in the sporangium. Next, the mother cell membrane
00:06:01.03		starts to migrate around the forespore, eventually fully engulfing it,
00:06:07.09		and then pinching it off as a free cell in the sporangium.
00:06:14.01		So, how does this process of asymmetric division take place?
00:06:18.17		Well, bacteria divide by means of a tubulin-like protein called FtsZ
00:06:27.01		which forms a cytokinetic ring known as the Z-ring.
00:06:30.09		Higher cells rely on actin, bacteria rely on tubulin.
00:06:35.12		Here is a fluorescence micrograph showing the Z-ring,
00:06:39.20		which has been tagged with the green fluorescence protein.
00:06:42.18		It’s in the center of the cells and it’s at the future site of cell division in a vegetatively growing cell.
00:06:49.16		So, when cells are growing, a Z-ring forms in the middle
00:06:52.21		and it’s then converted into a division septum
00:06:56.03		to give rise to two equal sized daughter cells. But when cells enter the pathway to sporulate,
00:07:02.25		what happens is that two Z-rings form. One near each pole of the sporangium.
00:07:09.08		And then only one of these two Z-rings gets converted into a division septum
00:07:15.17		whereas the other one is disassembled.
00:07:17.26		So that at the end of the process we have a single polar septum
00:07:22.01		that's created the two unequal size cells.
00:07:25.05		Now, immediately this raises interesting issues about how
00:07:29.10		each of these two cells acquire a chromosome.
00:07:31.28		The pre-divisional sporangium has two chromosomes and the challenge for the developing cell
00:07:38.29		is to ensure that the forespore and the mother cell each inherit a complete chromosome.
00:07:46.09		Sporulating B. subtilis goes about this process in a fascinating way
00:07:51.07		that differs from almost all other cell types that we know about.
00:07:55.14		Here is a cartoon that illustrates what the chromosomes look like in a growing cell.
00:08:02.29		They're in two masses referred to as nucleoids,
00:08:07.04		and each chromosome, of course, has an origin of replication
00:08:11.29		and the origins are at the outer edges of the two DNA masses.
00:08:16.01		When the cells enter the pathway to sporulate, those two DNA masses get remodeled into
00:08:22.17		a filament, known as the axial filament, that extends across the cell
00:08:27.21		from pole to pole with each of the two origins at the extreme opposite poles of the sporangium.
00:08:35.22		You can see this in this fluorescence micrograph, in which the DNA in this slide
00:08:43.07		is labeled in green and the outline of the cell in red.
00:08:47.20		In the growing cell you can see two distinct DNA masses
00:08:51.26		and in the cell that's begun to sporulate you can see that the DNA is
00:08:57.10		elongated and is extending all the way across the cell.
00:09:03.06		And the interpretive cartoon shows that the origins are at
00:09:06.21		the extreme opposite poles of this axial filament.
00:09:11.14		How does this happen? Well, this process of remodeling the chromosome into a filament and
00:09:18.27		anchoring it at the poles is mediated by two proteins.
00:09:22.06		They're called RacA and DivIVA. RacA binds to the DNA at multiple sites to collapse it
00:09:31.11		but especially around the origin to create a kind of Velcro that will stick it
00:09:37.04		to DivIVA, a protein which is anchored at the poles of the cell.
00:09:41.22		So you can see that in this cartoon. DivIVA is at opposite poles of the cell.
00:09:48.04		Here are the two DNA masses.
00:09:50.03		When RacA appears, it binds at diverse sites around the two chromosomes
00:09:55.23		to help collapse it, but forms a structure with many RacA molecules
00:10:01.20		at the origin regions. And as depicted in this cartoon, the chromosomes get stretched out
00:10:08.03		and adhere to the poles. Let me show that to you one more time. Here's the RacA protein,
00:10:13.24		and here's the process by which it gets pulled to opposite poles of the sporangium.
00:10:19.12		Now, finally, asymmetric division takes place.
00:10:22.20		But you'll immediately appreciate that when the division septum comes down,
00:10:27.16		because of its extreme polar placement,
00:10:30.08		only some of the chromosome destined to the forespore
00:10:34.05		will be in the little cell. So you can see this in these fluorescence micrographs.
00:10:39.19		Just after the division septum forms, only a little bit of DNA is in the forespore,
00:10:45.12		that which was trapped by virtue of being anchored at the pole. But then over time
00:10:50.20		the remainder of that chromosome gets pumped into the forespore compartment
00:10:55.20		until a complete chromosome is present in the forespore. This pumping
00:11:02.08		of a chromosome into the forespore is mediated by a molecular machine,
00:11:06.17		a protein called the DNA translocase,
00:11:09.17		which is located in the septum and uses energy from ATP
00:11:14.04		to pump the remaining portion of the chromosome into the forespore compartment.
00:11:19.18		So, most cells, or almost all cells that we know about separate their chromosomes prior
00:11:27.05		to cytokinesis. But, in sporulating cells, cytokinesis takes place before chromosome segregation.
00:11:34.10		We can visualize the DNA translocase that mediates this chromosome segregation by
00:11:39.24		tagging it with the green fluorescence protein shown in this cartoon.
00:11:44.00		So here's a sporangium, and you can see the polar septum
00:11:49.28		and this bright focus of green fluorescence
00:11:52.29		from the DNA translocase that's sitting in between
00:11:57.22		the mother cell and the forespore and is poised to pump DNA
00:12:01.10		across the septum into the small chamber
00:12:04.13		of the sporangium. So to review everything that I've said so far
00:12:10.24		in the very first stage of asymmetric division, the Z-protein is remodeled to form rings
00:12:20.16		at each pole of the sporangium. Then, one of these two Z-rings is converted into a division septum
00:12:26.21		and the other Z-ring is disassembled.
00:12:28.28		Next, chromosomes need to be segregated into the two cells.
00:12:36.20		And so while the Z-rings are forming, the two chromosomes are remodeled
00:12:41.21		into an axial filament by the RacA protein, which causes them to collapse
00:12:46.29		into elongated filament and anchors the origins at the poles,
00:12:51.04		where the DivIVA protein is present.
00:12:52.24		Then asymmetric division takes place, and the DNA translocase located in the division septum
00:12:59.11		pumps the remainder of the forespore chromosome into the small chamber of the sporangium.
00:13:05.25		So that when this process is complete we have two cells that lie side by side;
00:13:11.06		each has a complete chromosome. In the next stage of development,
00:13:17.21		the mother cell membrane migrates around the forespore
00:13:21.22		to fully engulf it and pinch it off as a free cell within a cell. So now the process of sporulation
00:13:30.02		is well underway and that inner cell will mature into a spore. This conversion of that inner cell
00:13:36.12		into a spore involves three principle, morphogenetic processes.
00:13:42.02		One, is the remodeling of the chromosome of the forespore into a doughnut-like structure,
00:13:47.15		in which state it’s highly resistant to radiation. The second is the formation of a thick
00:13:53.20		layer of cell wall material called the cortex around the forespore.
00:13:58.12		And then a thick protein shell made up of
00:14:02.06		many different proteins that creates a protective shell
00:14:05.27		around the spore. This next cartoon illustrates these processes.
00:14:11.11		So you'll see the forespore chromosome being remodeled
00:14:14.19		into a doughnut. The white area is the cortex,
00:14:18.04		and the thick protein shell of coat proteins is created on the outside.
00:14:23.10		This, then, matures into a spore, a golf ball-like spore. The mother cell, having done her job
00:14:32.05		lyses and liberates the mature spore, which can remain inert
00:14:36.16		for many years, but on a moment's notice, when
00:14:40.05		good conditions return, it can crack open like an egg, and give rise to a cell
00:14:46.09		that can resume vegetative growth and binary fission.
00:14:53.19		OK, so we've seen now how during sporulation, two cells are formed.
00:14:59.16		And the key point is that each of these two cells needs to follow its own distinct program
00:15:06.23		of gene expression.  These two cells have their own pathways of cellular differentiation,
00:15:11.29		the forespore and the mother cell.
00:15:13.10		These pathways of differentiation are driven by transcription factors
00:15:18.19		that act in a cell specific manner and that's the topic I want to talk about now.
00:15:24.08		So, in this cartoon I've indicated the five principle
00:15:31.15		transcription factors that drive the process of sporulation.
00:15:35.25		The first one is known as Spo0A and it’s the master regulator for sporulation.
00:15:41.24		It’s the protein which becomes activated in response to nutrient limitation
00:15:47.03		and causes the cell to enter this pathway and causes all the events
00:15:52.07		that I've been talking about to unfold, including asymmetric division.
00:15:56.04		After asymmetric division takes place,
00:15:58.13		then a transcription factor appears that's called sigmaF.
00:16:03.19		SigmaF is a member of a family of regulatory proteins
00:16:08.13		in bacteria known as RNA polymerase sigma factors that work by
00:16:12.14		binding to RNA polymerase and directing it to particular kinds of promoter...
00:16:17.17		promoter sequences in the chromosome.
00:16:20.13		The first of these sigma factors, sigmaF, becomes activated in the forespore compartment.
00:16:26.28		Then, a sigma factor called sigmaE gets activated in the mother cell compartment.
00:16:33.01		Then, after engulfment takes place, sigmaF gets replaced in the forespore
00:16:38.02		by a transcription factor called sigmaG.
00:16:40.23		And then lastly, in the mother cell, the final transcription factor
00:16:46.23		in the developmental program, sigmaK, appears.
00:16:50.00		That these transcription factors act in a cell specific manner
00:16:55.01		can be seen in the inset on the right.
00:16:58.09		Here I show you single sporangia that harbor a fusion of the gene for the
00:17:05.00		green fluorescence protein joined to a promoter under the control of sigmaE
00:17:09.26		in the top example or a promoter controlled by sigmaG in the bottom example.
00:17:14.16		You can see in the upper case fluorescence is restricted to the mother cell,
00:17:19.26		the compartment in which sigmaE is active.
00:17:22.14		Whereas in the bottom example, we have the opposite pattern.
00:17:26.09		The fluorescence is accumulated in the forespore compartment
00:17:29.09		where sigmaG is active.
00:17:31.22		So each of these four sigma factors act in a cell specific fashion.
00:17:36.05		And each one of them has presented a puzzle as to the molecular mechanisms
00:17:40.27		that cause it to become activated in a specific cell type.
00:17:45.06		We've, over the years, helped to unravel these mysteries
00:17:51.10		and figure out how these four transcription factors are activated.
00:17:54.23		And let me tell you just one story about what we know about the activation of sigmaF.
00:18:00.22		So, sigmaF as you've seen is activated in the forespore
00:18:05.14		but it’s actually synthesized and present in the pre-divisional sporangium.
00:18:10.01		It’s not active in the pre-divisional sporangium because it’s held inactive
00:18:16.11		in the pre-divisional sporangium by an antagonistic protein called AB.
00:18:21.09		AB is a so-called anti-sigma factor that binds to sigmaF and holds it in an inert state.
00:18:28.28		AB holds sigmaF inert in the pre-divisional cell and also
00:18:34.09		after asymmetric division in the mother cell.
00:18:37.06		But in the forespore, sigmaF manages to escape from AB and
00:18:41.27		becomes active in directing gene expression.
00:18:44.29		How does it escape?
00:18:46.12		Well, its escape is mediated by another protein that we call AA.
00:18:51.08		AA is an anti-anti-sigma factor that reacts with a complex of AB and sigmaF
00:18:59.20		to discharge free and active sigmaF.
00:19:03.23		AA itself is regulated by phosphorylation.  It’s a phospho-protein and
00:19:10.01		in its phosphorylated state it is inactive and in its dephosphorylated state
00:19:15.28		it’s active and capable of triggering the activation of sigmaF.
00:19:20.04		This conversion from the phospho-form to the dephospho-form is mediated by
00:19:25.23		a phosphatase called E. So E converts AA-phosphate to AA.
00:19:33.07		And then AA reacts with AB-sigmaF to discharge
00:19:38.08		free and active sigmaF in the forespore compartment.
00:19:41.09		How does this happen just in the forespore?
00:19:44.04		Well, we don't fully know the answer to this question.
00:19:46.21		But undoubtedly, an important clue is the discovery that the E phosphatase
00:19:53.09		is itself situated in the septum that divides the two cells from each other.
00:19:58.08		So here we've tagged the E phosphatase with the green fluorescence protein.
00:20:03.08		You can see that in the left fluorescence panel.
00:20:05.27		And in the right fluorescence panel we've stained the sporangium membranes with
00:20:11.05		a red membrane dye. And you can see that the E protein is located right in the septum.
00:20:17.07		Somehow, it acts preferentially or exclusively on the forespore side of the septum
00:20:23.12		to cause sigma F to be activated in that compartment and not the mother cell compartment.
00:20:29.13		So let me bring everything I've said up until now together;
00:20:33.01		AA, AB, activation of sigmaF, using a field of cells
00:20:39.27		in which each cell harbors a fusion of the gene
00:20:44.04		for the green fluorescence protein to the promoter
00:20:46.21		to a promoter under the control of sigmaF.
00:20:49.14		So as this movie begins you can see that all of the cells are dark;
00:20:54.10		they have no fluorescence. Then asymmetric division takes place.
00:20:57.28		And then sigmaF becomes activated and you can see the bright green foci appearing
00:21:02.16		massively in the cells in this field as they begin to sporulate.
00:21:08.03		Then those bright green foci get converted into opaque phase bright bodies
00:21:14.10		as sporulation is completed. Let's look at this one last time.
00:21:18.05		Here's the field of cells, then massively, green fluorescence appears
00:21:22.28		near one end of each of those sporangia.
00:21:26.12		And then those green foci become phase bright bodies that represent the maturing spores.
00:21:35.03		OK, let's now come to the last topic.
00:21:38.25		I may have left you with the impression up to now that after asymmetric division
00:21:43.18		the forespore and the mother cell each march to their own drummer,
00:21:48.02		independently follow their own independent programs of gene expression.
00:21:52.05		But nothing could be further from the truth,
00:21:54.10		because the two cells are having a conversation with each other
00:21:57.29		at each stage of development. They talk back and forth
00:22:01.06		to each other so as to coordinate the progress of development in one cell
00:22:06.13		to the progress of development in the other cell.
00:22:09.03		So, to begin, as we've seen sigmaF is activated in the forespore compartment.
00:22:16.01		But sigmaE does not appear until sigmaF is active.
00:22:21.14		SigmaF sends a signal across the membranes that separate the two cells
00:22:27.24		that leads to the activation of sigmaE in the mother cell.
00:22:31.04		Once sigmaE is activated in the mother cell, it in turn sends another signal
00:22:36.13		that leads to the activation of sigmaG in the forespore cell,
00:22:41.16		the now engulfed forespore compartment.
00:22:43.22		Once sigmaG is activated, it in turn sends a signal back to the mother cell
00:22:52.05		that allows the final transcription factor in this sequence, sigmaK,
00:22:57.12		to appear. So the two cells are talking to each other
00:23:00.27		in a two-way conversation: from forespore to mother cell,
00:23:05.04		to mother cell to forespore, to forespore to mother cell.
00:23:09.06		Let's listen in on one of these conversations
00:23:12.26		and see just how the language of one of these conversations between the two cells
00:23:18.14		the very last one, in which sigmaG tells the mother cell to activate sigmaK.
00:23:23.11		The way this works is as follows:
00:23:26.10		sigmaK is initially synthesized as an inactive pro-protein.
00:23:31.12		That is, the primary gene product has an N-terminal extension
00:23:36.00		of about 20 amino acids that renders pro-sigmaK inactive.
00:23:41.25		In order for it to be active a protease needs to chop off that N-terminal extension
00:23:48.11		to generate the mature and active form of the transcription factor.
00:23:52.20		You can see that in this Western blot experiment.
00:23:58.00		So this is an experiment in which all the proteins from the sporulating cell were
00:24:01.17		separated on a gel and then sigmaK and pro-sigmaK were visualized
00:24:07.12		with antibodies to the protein. And as you can see in a wild-type sporulating cell
00:24:13.29		most of the sigmaK is in the form of the mature and active protein
00:24:18.27		and relatively little in the larger pro-protein form.
00:24:22.29		This conversion of pro- to mature depends on the action of sigmaG.
00:24:28.19		And you can see this key point if we use a mutant of sigmaG.
00:24:34.24		When sigmaG is mutant there is no conversion and if you look at the Western blot
00:24:39.25		analysis on the far right of the mutant, now you can see that all of the protein
00:24:45.12		is in the pro-form and little or none is in the form of the mature sigma factor.
00:24:50.10		Somehow, the activation of sigmaK in one cell, depends on genetic events
00:24:56.15		taking place in the adjacent cell. How does this work?
00:25:00.26		Well, the protease is a membrane protein and it mediates the cleavage of the pro-sequence.
00:25:09.13		But initially it’s held inactive by two other membrane proteins
00:25:15.03		that are inhibitory and together hold the protein in an inactive complex.
00:25:20.22		In order for the protease to become activated,
00:25:24.28		the protease needs to escape from this inhibition.
00:25:28.21		And that event is caused by a signaling protein
00:25:34.04		that's produced in the forespore compartment under the control of sigmaG.
00:25:39.12		So sigmaG turns on the gene for a signaling protein,
00:25:42.15		that signaling protein is secreted across the membrane
00:25:46.16		of the forespore where it interacts with a complex of proteins
00:25:51.27		that includes the protease and its inhibitory proteins
00:25:55.07		and reverses the inhibition so that now cleavage of
00:25:59.18		pro-sigmaK to the mature form of the transcription factor can take place.
00:26:04.23		This protease turns out to be especially interesting on two counts.
00:26:10.13		First, we infer that its active site is located in the membrane.
00:26:15.16		The blue bars represent the inferred catalytic regions
00:26:20.18		of the protease and it’s inferred that the N-terminal extension on sigmaK
00:26:25.25		inserts into a cavity, in the membrane, created by the protease.
00:26:30.25		Well, this kind of membrane cleavage leading to gene... activation of gene expression
00:26:38.17		is a fore-runner of something that's widespread in biology
00:26:42.19		and is referred to as regulated inter-membrane proteolysis.
00:26:46.11		And interestingly, this very example of it in a bacterium
00:26:51.26		is conserved all the way up to mammals.
00:26:54.09		Mammals have a protease with homologous features, in particular the catalytic center,
00:27:01.15		to the bacterial protease. In the case of mammals,
00:27:06.03		the protease activates a transcription factor that's bound to the membrane
00:27:11.07		and cleavage by the protease releases it from the membrane
00:27:15.02		and so it can migrate to the nucleus and activate gene expression,
00:27:19.22		in this case, genes involved in cholesterol metabolism.
00:27:22.22		But, the overall principle is the same.
00:27:27.21		Two transcription factors are in inactive states that require proteolysis to be activated
00:27:33.22		so that they can turn on genes.
00:27:36.21		And the similar proteases, conserved over eons of evolution, mediate both processes.
00:27:44.09		So finally, let me point you in the direction of future research:
00:27:51.00		what I see as a principle challenge for the future.
00:27:55.13		We've talked about the cell biology of sporulation, and we've talked about
00:28:00.27		the orchestrated expression of genes under the control
00:28:05.15		of a series of cell-specific transcription factors.
00:28:08.20		These transcription factors are activating over 500 genes
00:28:14.26		in a cell-specific and temporal fashion. And it’s the products of those genes
00:28:21.18		that mediate the morphogenesis that culminates in the spore.
00:28:25.27		So the final challenge is to understand how the myriad proteins
00:28:31.15		produced under the control of sigmaF, E, G and K mediate morphogenesis, drive
00:28:39.07		the assembly of the spore into this remarkable dormant structure that can resist
00:28:45.18		the ravages of time and insults of the environment in such a robust manner.
00:28:52.04		Thank you.

This material is based upon work supported by the National Science Foundation and the National Institute of General Medical Sciences under Grant No. 2122350 and 1 R25 GM139147. Any opinion, finding, conclusion, or recommendation expressed in these videos are solely those of the speakers and do not necessarily represent the views of the Science Communication Lab/iBiology, the National Science Foundation, the National Institutes of Health, or other Science Communication Lab funders.

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