(casual music) - My lab is really
interested in understanding how different organisms in
animals associate with microbes. So, one part of my lab studies. Some of the really nitty gritty details about how surfaces of different bacteria recognized by us and other organisms. And then another part of
my lab studies this problem and the context of ticks. And the reason that ticks
are such great systems for study for us is that
ticks have very specific relationships with different microbes. So the pairings are incredibly restricted which is also part of the reason why they transmit a lot of these to us. And so we're interested
in using this to study and also just really to understand
how they're transmitted. And try and get a handle
on that biomedical problem. So, I'll just preface
this by saying two things. One is that one of the
best ways to prevent tick-borne diseases is through education. So I really am super happy
that you guys are here tonight. Second is that I'm supposed
to take questions at the end about the substance. But if there are any
clarification questions that come up throughout. I would be very happy for
you to raise your hand and ask 'cause I think
that's really important for us to make the most out of our time. Okay so, let's learn a little bit about blood feeding arthropods. So what we see on the
screen are things that you probably have encountered
in your life at some point. We have mosquito, a sandfly and a tick. And what these things
have in common for us is that they're vectors for disease. So what do I mean by vectors for disease? It means that they naturally have microbes in their bodies, normally in their guts. That when they bite us it
passes through them into us and then they can transmit
microbes that are really dangerous to our health. So, here's some really classic examples that you might recognize,
the diseases that they cause. Mosquitoes can cause malaria. Sleeping sickness is caused by flies. And then on the right which is
gonna be the focus for today is the blacklegged tick,
also known as the deer tick. Ixodes scapularis that causes Lyme disease when it bites you and
transmits a bacterium called Borrelia burgdoferi. So I'm gonna go through a couple
of different topics today. I'm gonna start by telling you a lot more about just the biology of ticks. And what makes them so
good at transmitting pathogens to us. And then I'm gonna talk a little bit about some of the challenges that are associated with diagnosing and treating Lyme. I know that this is a really hot topic and it's actually a
very complicated topic. So I'm just gonna try
and give you an overview of some of the challenges. And then I'm gonna talk a little bit about the strategies that
people are thinking about and implementing for
blocking tick-borne diseases. And then a little bit more about what else can we learn from ticks just
by studying their biology. So I'm gonna try and also
sprinkle in a little bit of information throughout
of research that's happening in the field and in my lab to inform you on the newest research. Okay, so ticks are vectors
for a lot of human diseases. So what you see here on
the left and in the text are different types of ticks. And there's hundreds of
different tick species out there. And these are ones that are most commonly associated with human disease
here in the United States. So I have the species
name next to each one. You can see they look quite different and each of them carries a
different set of microbes. And that's as I eluded to
earlier something my lab's really interested in. And these microbes mean that
they cause different diseases. And so what you can see here
in the red text on the right are the diseases that are
caused by each of those different ticks. And so they're categorized
based on the ticks that are able to transmit
these different pathogens. And so what you can
already see here is that there is specificity to this. So one of the first things
that you can learn about to help prevent or to
understand what you could be infected with is to just understand that it really depends on what tick bit you. If you can take a picture or
look up what species it is. It really helps you narrow
down the range of microbes you may be infected with. Okay so, what these ticks have in common is that they're known as hard ticks. And this Ixodes scapularis
which causes Lyme disease is in fact a hard tick. There's also a whole other group of ticks that I'm not going to talk about tonight But which is worth knowing
which are the soft ticks. And here's an example of one on the right. I actually think they're
quite gross looking compared to my favorite tick. But there're also some really
key biological differences that affect the way
they interact with this and what they can transmit to us. The first thing is that
the hard ticks on the left have a hard outer shell. So not the most creative
name, it's called a scutum. And you can see this kind
of dark brown circle, that's what the scutum
arrow is pointing to. And they also have feeders called, an organ called the capitulum
which is extending out. It kind of looks like this
drill at the top of a tick. The soft ticks have
one too but it's hidden a little bit below the
picture so you can't see it. So those are some of the major sort of physiological differences. And the reason that they
have really unique physiology from each other is that they also feed in a really different way. And that's going to matter as we go on in terms of how they move
their microbes into us. So hard ticks here on the left. The reason that they're hard
is they have a really unique outer layer that completely remodels as they engorge and fill up on blood. And they engorge on a lot of blood. So what they do is they
take their capitulum and they push their feeder into your skin. And they create what's called
a pool to suck out blood. Kind of like a straw
where the bloods pouring into this little pool and
they're feeding out of your skin. The soft ticks are different. They feed for shorter periods of time. And they puncture your skin
and the blood that comes out they kind of lap it up. Which is why I have here
a spoon and a bottle to kind of give you a schematic idea of how they're different. And so because the hard ticks on the left feed on you for so long. We call them prolonged blood feeders. They can stay attached
in your skin for days to sometimes over a week. So they really take their time to nest and make a home in your body. And that affects the range of microbes they can transmit to you. So ticks are actually quite incredible compared to all the different
blood feeding arthropods. Mosquitoes, flies, et cetera. And that they can transmit an incredibly diverse set of microbes because they're in your skin for so long. And so I'm gonna zoom in on this particular species of hard tick. I will say that there is
slightly different features of the biology depending
on which hard tick. But because we're gonna
talk a little bit more about Lyme disease today. That's what I'm gonna focus on. So a few basic facts. They have three distinct life stages. Larvae, nymphal and adult and
they get bigger with each. And in between each these
ticks need a single blood meal. And so that is critical
for them to transition to the next life stage and it's long. It's about days to a week
depending on the context. And so in between each these
blood meals can last for a really long time. And during this period they
can transmit things to you. So what happens in the
life stage of the tick is that the larvae ticks. They actually don't carry
the Lyme disease pathogen, they are what we call naive. And so when they feed on small rodents that are carries of Borrelia burgdoferi which is the pathogen. That gets into the gut of the tick and then they drop off the rodent. And they molt into the next life stage. And that bacterium stays
in the gut of the tick across that molt. And it's in the latter life
stages that when they bite you they can transmit it from the
gut into the salivary glands and spit it back out into
you though their saliva into your bite site. And so that's the normal
mode of transmission and it's associated with
this classic bulls eye rash. But that's not associated
with all patients and we'll talk about
that a little bit later. But it has become an increasing
public health burden. Cases have more than tripled
in the passed decade. You've probably been hearing
more and more about it in the press. And in the United States
proper, it's the most commonly reported vector born disease. Meaning that it's the most
commonly reported thing that gets transmitted through
some sort of arthropod. And so of course Malaria
is a huge problem globally but within the United States
this is very problematic. So Lyme disease cases are on the rise. And so it's interesting
to think more about the biology of the tick
and why they're so unique in their ability to transmit this. Because maybe that could
provide us with clues as to how we can block it. Because this pathogen
completely relies on the tick for entry and spread in your body. And so as I mentioned
at the start of this, tick pathogen relationships
are very specific. So what we have here is a map from the CDC showing all the different
parts of the Unites States where there has been confirmed
cases of Lyme disease. And so you can see there's
a huge clustering over towards the right side of that map. So thank goodness we are on the left side. And I was very happy to see that Hawaii is still as wonderful of a
place as you want to believe. And so the reason I want to point this out is that part of the reason
that this is so restricted is that the vector tick for this. The species that can carry it is also geographically restricted
to that side of the US. And you'll note that
there were a few cases on the west coast and
that's for a few reasons. Number one, people do
travel which is adding, that globalization is
really adding to the ability of ticks to move with the
people to different places. You know, they don't always
necessarily bite you right away. They may hang out for a while
finding that perfect spot to dig in. And so they can travel with you and they can definitely travel with pets. The second reason is that
we do have a tick out here that can, in theory,
transmit the Lyme disease pathogen to us. And that's what we in our
lab think of as a sister tick which is Ixodes pacificus. It's more commonly known as
a western blacklegged tick. And it looks, you know to a new person, very similar to Ixodes scapularis. So this tick, if we were to
take it through lab experiments. It intrinsically can carry and
transmit the Lyme pathogen. What makes it special
compared to scapularis and why we're somewhat
protected form Lyme disease incidents out here. Is that they have a
strongly preferred host of the western fence lizard. You may have seen this in your backyard. They're about this big and
they're just all over California. And we don't completely understand why they prefer this so
much more than rodents. But if you present them with both they always go to the lizard. And that's significant because this lizard does not carry Borrelia. There are squirrels out
there that do carry it but because ticks will
always go to lizards as long as they're there. We don't usually, we aren't usually at risk for transmission. And so something about the lizard blood is antagonistic towards this pathogen. We call it Borreliose
idle because it is able to really clear Borrelia effectively. In fact there was someone at Berkeley who studied this many years ago, Bob Lang. And I have a student in my
lab who's also interested in picking this project back up. And trying to figure out what it is about this lizard blood
that is so Borreliose idle. So, I think there could be
a lot of interesting lessons coming out from that. So here's just a picture
of someone in my group when we went out to
basically lasso up lizards and you can pull the ticks off of them. And you can see the picture on the right. It looks like almost like a gray pearl earring on the lizard. That is an engorged tick. And so we can find dozens
of those, at least, on the lizards out here. Especially in the Spring
when you can literally just pull them off. And so one of the things we're
doing is pulling them off their natural host out here. And seeing what kind of microbes
are in their guts to try and get a better picture of
what's happening in California compared to the east coast. So, in addition to some of
the work that my lab is doing on this. I wanted to highlight
some work by Nate Nieto. He actually passed away very recently but he's done some incredibly
useful work for our field. And he's been supported by
the Bay Area Lyme Foundation. So we're very appreciative of his efforts. He started a project
that is still ongoing. And I would highly encourage everyone to let your friends know about it. It's called the Citizens Science Project. And this project aims
to look at what ticks people are actually pulling
off of them or their pets. So it's kind of an
advance beyond just saying what do the ticks out there carrying? But what are the ticks that we're actually running into carrying? Because that may be slightly different from just a random field
study where we're dragging and trying to collect
things that are out there. And so what he's done
is have people send in from all over the country. Ticks that they find on
them, they send it in. And they've been looking at
what's inside of the ticks. And I will say one of the things that was really interesting about this study is they found that people with
pets are at higher risk for tick-borne diseases. And that's because sometimes
pets will track these ticks in. Which may or may not
bit the pets right away. And so there could be a
delay between your activity and when a tick gets on you. And that obviously will
put you at more risk if you're not really
paying attention to when and where you have a tick on you. So a few just highlights from this study that I wanted to point out. So this is, it has been really successful. What this heat map is
showing is the number of Ixodes ticks that have been
collected from citizens all over the country. And you can really see the
concentration on the east coast but we're getting a lot
of information also about Ixodes specific on the
west coast which is great. Has anyone in here gotten a
tick on you while out hiking? Okay, great. Well, not great but they're out there. They're out there. (laughing) There's a lot of other species
and I want to make sure to recognize them as well
because they are not always on our radar. But some of these, for example. Dermacentor is known as
the American dog tick. So it's really commonly found on pets. But they are also
scattered throughout the US and just being very aware. This is all information
that's publicly available. Educating yourself on
what ticks are in the area that you're in. Even if you're traveling you
could just check, you know. If you're hiking in a
park what's out there so that you can prepare
yourself to pay attention to whether you have a tick on you. What kind it is? And if you have any symptoms
because early detection is really important. And so I also have some zoomed in graphics of the ticks that we
found in the northeast. The majority of them
were Ixodes scapularis but there were many other
submissions as well. So this really allowed for
us to look at the patterns of interactions of humans with ticks. And so that is what my
next graph is showing is the submissions across time. So a longitudinal comparison
of when people are getting it. And what you can really see is that there's a burst with the seasons. And what that is are the life
stages of the tick really. What you have are larvae
nymphs and adults. And so the reason I
wanted to point this out is that it is important
to know when they're out because that is also a risk factor. But it's also important to know that larvae are generally naive for Borreliose. So the nymphs and adults are really what you're looking for. And nymphs are the ones that are the most common
transmitters of the pathogen because they're usually
out in the summer time. Or the spring time when you're also out running into their ecology. And also the adults are just
a little bit easier to see and pick off. So the functional outcome of that is that it's typically the nymphs. So we're really interested
in thinking about Ixodes scapularis. But also the differences
between scapularis and pacificus in terms of thinking about what's happening on the
ground in California. And this is just to iterate
that the two species, although they have a lot of similarities. Their behavior and their
biology is also quite different. They feed on different things. The timing of when
they're out is different. And even our collection
strategies out here on the west coast are
slightly different in terms of where we think we might find them compared to the east coast. And so these ecological
factors in addition to the intrinsic ability
of the ticks to carry and transmit together are
known as vector capacity. And so one area of study
in my lab is moving beyond the ecological factors
and thinking more about the intrinsic factors which
is called vector competence. And these are principles
that apply to not just ticks but any other vectors that people study. So vector competence means
that these ticks have the intrinsic ability to carry. Acquire, carry and transmit
all of these different things and I'll explain what I
mean by that in a second. So that means even in the lab when we can carefully control it. There are some ticks that
you can feed them on mice that are clearly infected. Or even inject the pathogen into them but they're unable to carry
it and transmit it into you through their bite. And so that is something
that we're very interested in is studying each of these
different points of transmission that are critical for that
to happen successfully. So I'm gonna walk you through
what I mean by all of that. By first walking you through
the transmission cycle which I mentioned to you earlier. So ticks have these three life stages. Larvae, nymphal and adults. And the larvae acquire the
pathogen through the rodents which we call reservoir animals because they serve as a reservoir
for the pathogen. That the ticks keep feeding on them and the natural life cycle. That's how persistent
a population of ticks. And so we are actually a dead end host. We are not good host for Borrelia because the likelihood
that they can keep on continuing their life
cycle through us is poor because it's symptomatic for us. For the bacterium it's
preferable to continue in the natural life cycle for the rodent which is asymptomatic. So everybody's actually
functioning in total harmony. It's when we enter into their ecology and interrupt that that the
bad things happen to us. Because we have not evolved
to be hosts for this pathogen. So the nymphs as I mentioned
will quest and find you. And by the way, they do not fly or jump. That was something that
I have had to clarify to a lot of people. But they're really good at finding you. And the way they find
you is they do something called questing. So that means that they
climb up to the tops of grass or shrubbery. Regions where they could
easily latch on to an animal walking by. And they literally just
raise their arms up. In the lab we have tubes of ticks and when I open it they crawl to the top. And they look like they're
looking for a hug or something. A little bit cute from my perspective. I'm sure nobody else would think that but. (laughing) But they basically have these sticky legs that they can latch on to an
animal when it's walking by. And they have ways to sense
when an animal is walking by through temperature, through
things in perspiration. And humidity is also cue for ticks. And so if they don't sense those
things they're quite still. They're trying to conserve their energy and then they latch on
when an animal walks by. So that happens and then they
find their favorite place to really dig in. And then a few classic things
have to happen across space and time for transmission to occur. So the first thing that
happens is that ticks burrow in and they secrete through their saliva these cement like substances
that build a cone. Which we call a poll into your skin and it goes all the way
past the outer layer down into the dermis. Where the blood vessels
are pouring blood into that and they're drinking it out of that pool. And so it takes about a day
for them to properly build that pool. And then after the blood starts entering, it takes at least abut a day. Then as the blood enters into the gut there's a burst of
replication meaning that the bacteria suddenly start
to expand their population. And then after a period
of time the bacteria that are expanding in
here are able to move across tissue layers in the tick. They can move out of the tick gut into the salivary glands. Which is a completely
different organ for the tick. And then that's how they're regurgitated back into your bite
site through the saliva. So it really has to
happen through the spit. And there's an amount
of time that has to pass before each of these
steps can be completed. And so that's one really
important thing to remember for the Lyme pathogen. Which is that if you've only had, even if it's the correct tick. If it's only been attached
for the day, for a day. You're risk of being infected is very low. Generally it takes about 36
hours or more for it to happen. The other thing that I wanted
to mention is just that each of these steps is really
specific to the vector. So even if a non-vector tick species. Which there are some
Amblyomma ticks, for example, have been. That they found Borrelia
in the gut of the ticks. But for whatever reason
Borerelia just doesn't expand its population as
effectively in this other tick and so that's subpar. The other thing that's
subpar is that very few. Usually no bacteria
can make it all the way into the salivary glands. So that doesn't happen. These ticks are not like
some other arthropods that kind of spit out through their gut. The gut contents, they have
to go through the saliva. So if it never makes it
into the salivary glands there's just no way Borrelia
will make it into you. And then finally there's inoculation which means that the
ability of it to inject it into your bite site and for it
to successfully both survive and then move into your body. That is a really key step
too which I'll talk about a little more at the end. But it's a cool phenomenon
because what people have seen is that the saliva of the
tick is really important for that to happen. It's not just the mechanical delivery because you can actually take a needle and inject Borrelia into skin. And your skin is very
effective at clearing it. But if you inject it together with saliva that we can take from a tick. It greatly increases the
ability of the bacterium to both survive and spread in your body. So these two are working
together like a real partnership and some of that is fairly
unique to the tick vector because you can take saliva
from the other species and the effect is not as strong. So these are like really
magnificent duo at every stage. I guess one other thing
I'll mention is that there's also something else
going on with the tick feeding in the opposite direction. Which is that the Borrelia
bacteria doesn't usually just float around in your blood. We don't refer to it as
a blood born pathogen because it's not always in your blood. It travels through your blood initially but it actually makes a home in tissues that are a little bit further away usually from where the bite site is. So when the tick's feeding
there's something about that that wakes up the bacteria
and causes them to migrate to the bite site. And the vector tick species
is really good at doing this. We don't exactly know
what the signals are. A lot of people in the field
are really interested in it. But there's some real long
range signaling that's happening between the tick and
the host that's causing the bacteria to sense it and come. And it's dramatic
sometimes where in the lab if we feed non-competent
tick species on a mouse. They really won't get
very many of the bacteria to the bite site. But if we feed both of
the vector, this tick and the non-vector
ticks on the same mouse. Everybody gets more and that's because there's something about the species that allows more Borrelia to travel. And so we think it's
really cool that, well. You know, it's unfortunate
that this happens but it's really interesting to think about how this happens so uniquely
with this particular tick. And one of the things
my lab and other groups really want to understand
is what are the molecules that are involved in
allowing this to happen? Or maybe conversely what are the molecules is the other tick species that are preventing this from happening? If we can figure some
of those mechanisms out. That might be a handle for us to try and block this since it's so
reliant on the tick vector. Okay, so I wanted to briefly talk about some of the challenges
associated with diagnosing Lyme. This is one of the most
problematic aspects of the disease. Is being able to accurately
and quickly diagnose patients who have been exposed to Lyme pathogen. And so I'm gonna talk a
little bit about why that is. So here again is Borrelia burgdoferi. And I had mentioned earlier
that the bite of the tick carrying Borrelia can often
lead to this bulls eye rash. Which everybody has
probably seen at some point or heard about. The problem with that is a couple things. If a tick bites you lets say in your hair which happens a lot. Ticks are quite good at going to places that you're not paying
attention to or your back. You may not see it right away
or you may not see it at all. The second thing is this
doesn't happen for all patients. It happens to about half of the patients. So that means if you don't have this you may assume that everything is fine. You may never even notice the tick. And then you're just living
your life like normal. The symptoms that can
rise from Lyme disease are also really diverse. And some of them can be associated
with many other diseases. So arthritis, fatigue and
these can sometimes ultimately lead to neuro degeneration and be fatal. But it takes a really long
time so you can imagine. I actually have started having some knee and back problems in my mid 30s. So I wouldn't necessarily think that I had a tick infect me with this. It may take a really long
time for me to realize that there's something wrong. And it may also take a long
time for these symptoms to come up because ticks can incubate for a really long time
before they really start to proliferate in your body. And so the other thing that
I mentioned earlier was that they move through your blood
but they ultimately reside in tissues. Some of which are very immune privileged. And so there's a limited
window for treatment because they're not just in your blood where we can give normal drugs
to people like antibiotics that are often very effective for microbes that are in your blood. For sepsis and what not. But this is a little bit
harder to get enough drugs to the right place to be effective. So the longer you wait
between when you're infected and when you treat. The less likely it is going to be that the antibiotics are effective. So this is a really problematic
aspect of Lyme disease. And it's also just very
difficult the detect. Even if it is in your blood
the levels are quite low. And so there's a lot of
interest in trying to figure out if there's a way to rather than looking at the cells that are actually in your blood. Your body's response to
this pathogen as a signature that could read out that you
might be infected with this. So there are a lot of people working on different aspects of this. Some of the diagnostic tools
out there are exactly this. Looking at your immune reaction to that. Charles Choo is an
investigator here at UCSF. Who's been looking into new technology sequencing based technologies
to also find a read out for this for Lyme disease. You might know that
there's a vaccine for dogs but there's not currently
a vaccine for humans. I'll mention this a little bit later when we talk about
strategies for blocking. But there was a vaccine
that had been taken pretty far through the
process of getting approved. And then ultimately it failed before it fully went to market. So there's currently no direct way to treat Lyme disease specifically. Another challenge with tick-borne diseases that's beyond Lyme. Is that ticks can carry
more than one microbe. So I had shown you that
list at the very beginning of all the different
diseases they can transmit. That doesn't mean that a single
tick can only transmit one. Sometimes a single Ixodes scapularis tick can transmit multiple things. And so from that same study I
showed you from Nate earlier they looked at the
incidence of co-infections. And they did see examples of this, of it carrying multiple pathogens. And these are really just pathogens that we already know about. Although we think there could be others that we haven't even discovered. So this is kind of a candid approach but it's suggesting that it
can infect with more than one. So you can just imagine that this could really throw you off. For some of these there
are overlapping symptoms. And so Lyme is the most
commonly known one. You might be completely focused on Lyme when you could have something else or something else exasperating
the Lyme pathogen infection. And so that's all adding to the challenges associated with this. And so I'm gonna talk
about this more in a second but there's more interests now in also trying to block the tick itself. Rather than just trying to
go for specific pathogens. Like if you could take
out the deliver service you might be able to take
out all of the things it's delivering. And so I'm gonna go
through this for a bit. So there was a vaccine that came out. And I wanted to put up this article that was Nature Medicine in 2014. I don't have a ton of time
today to go through this in great detail. But it's a really interesting
and a not very long read. I highly encourage everyone to look it up and give it a read. But it talks through a lot of the sort of political logistic technical challenges associated with getting this
vaccine through the pipeline. One of which was it has in
quotes here, the Yuppie Vaccine. So, when they were developing this vaccine as they talk about in the article. There was this criticism
that this Lyme disease was really a disease that
only afflicted the privileged. It was the privileged
people who were going on these hikes in New England
that were getting it. That this shouldn't be a major
focus of biomedical efforts. And so that was one thing that kind of poorly branded the whole thing. And so that was an obstacle
but then there were also other technical obstacles that they talk about more in the article. But ultimately that really was
a big setback for the fields because there was this vaccine
that showed some efficacy. But a lot of researchers
were kind of discouraged by the outcome of this process. But you know, I think
that the researchers are still definitely sticking with it. And there's hope ahead that
there's a lot of groups that are trying to figure
out new ways to do this. One of the new ways is
called paratransgenesis. So this is talking about
controlling something about the biology of the vector
rather than going after the actual microbe. And typically it's by
engineering other microbes that are associated with
the vector that could negatively effect the
ability of the vector to carry the pathogen. I'll explain what I mean
by that through an example. So this is Aedes aegypti
which is the mosquito that can transmit Zika. Mosquitoes can also transmit
a number of other things. Dengue, chikungunya, yellow fever. But mosquitoes as do many
other insects have this what we call symbiont. Meaning it's a microbe
that's always associated with the insect. It has some sort of partnership
of itself with the insect. And the symbiont is a
bacterium called Wolbachia. It's very pervasive and
what researchers found is that certain kinds of Wolbachia that are associated with insects. If the insect has it,
it's unable to transmit some of the pathogens. So then they cleverly
thought well if we could just engineer the mosquitoes to have this and spread it through the population. We might find a way to
actually block their ability to be a vector. So that's the idea
behind paratransgenesis. And this has actually
shown some early success in mosquitoes. They've done a number of
releases of mosquitoes that are infected with this bacterium. With by the way has no
detrimental effect for us. And there's been some success
coming through the pipeline for this work. So I'd encourage you
to read more about it. In fact there was a release
in California a few years ago through a project called Debug Fresno. So this is an active area of research if you hadn't heard about it already. And so my group and
others are very interested in whether there's the potential to do something like that in ticks as well. So over the last few years has been really an outpouring of reports looking at all the different microbes
that are naturally associated with ticks
trying to identify things. That may negatively correlate
and potentially block the Lyme pathogen. And so I just wanted to
show you a few snapshots of the actual tick gut
that my labs looked at as a representative data set of looking at the microbes in ticks. Here is the tick gut. You can see the epithelial
cells which are basically the layer lining the tick gut. And then in the middle
as the lumen of the gut. So this is a cross
section through its gut. And the blue is staining all
the different tick cells. And then in magenta are
ways for us to stain the actually bacterium
that causes Lyme disease. It has this kind of cork
screw like shape to it. Squiggling along the lining of this. And then here it is
overlayed in black and white you can really see it popping. It's kind of just like snaking around the lining of the tick
gut waiting to go out with the blood meal coming in. And so what we can do is also
visualize other bacteria. What you can see in
this one is there's not that many other bacteria that are present besides this particular one. But some of the tick guts we
see something very different. Which is that we see these
tiny little dots here and you can zoom in. And this is a stain
specifically for bacteria where you can see kind of rod shaped and circular shaped
bacteria that seemed to be residing in the tick gut. And notably we don't see
Borrelia in this tick. So my lab and others are
starting to go through these individual species. And see if a lab controlled experiments we can replicate some of these patterns and block really a
transmission by the tick. And there's many other groups
working on this as well. So, in addition to this
there's another strategy that's coming to the fore in the field. Which is taking a page
from the playbook that people for the sandfly
field and mosquito field have taken as well. Which is thinking about
the biology of the tick. The saliva is really
important for the tick to finish its blood meal. And so if you can block saliva or something in it that's
critical for the tick. You may also be able to
block the successful movement of the pathogen through the tick. And so there's this vaccine in sandflies that's a vaccine against, not a microbe but against the sandfly saliva protien. And that in turn blocks
the ability of the sandfly to transmit what causes leishmania. And so this has been a
really exciting new develop in that field. And more and more people are interested in looking at what all is going
on in tick saliva as well. And ticks are incredibly
dependent on their saliva for their feeding. We happen to think that
tick saliva is the coolest of all the blood feeding saliva because they feed for so long. So that is another area
that we're starting to move more into, both my lab and
other labs in the field. Starting to go through and study
the biology of tick saliva. In tick saliva there's
hundreds of proteins compared to dozens or less that are in mosquitoes and sandflies. And that's because they
feed for so much longer. And so ticks are really
master regulators of us. And so what I'm showing you here if it doesn't gross you out too much is a tick that's actually in
the middle of its blood meal. And you can really see it is
like diving all the way in. This is not a passing interaction. And so has anyone had one on
them and not even realized it? Okay, it's the creepiest
feeling in the world. At least it was for me the
first time I found a tick on me because it's just in your dermis and you don't even realize it. And that's because ticks
are very very adept at shutting down your
ability to detect them. So their saliva does all kinds of things when they bite into you. And you can just imagine for a tick. Because they have this
one single blood meal to transition between their
life stages, it's so critical. That when they decide to
feed that it goes well. And so everything is geared towards this happening successfully. So here's just a cartoon schematic. They break through your
skin and they form this cone like cement layer. The blood vessels pour in. So if we think about this,
a lot of different things have to happen for this to
work out okay for the tick. Number one, when they
break into your bite site it's possible that some of the microbes around on your skin could
infect the bite site. And so that could cause
rashing or swelling. And just like anytime you have
a cut and it gets infected. So it has a lot of
antibacterials in its own saliva that some how Borrelia is able to evade. But these antibacterials help
to keep that bite site clean. The other thing is that it
blocks your ability to heal. So they have things that
prevent platelet aggregation or clotting. So the blood can really
flow freely into this site without incidence. In fact there's things that
promote active blood flow. It also has the ability because your skin, even if you didn't have an infection. Obviously if you scratch it,
we've all had a bump come up. It prevents that from happening
so it prevents inflammation. So it has anti immunity
things that shut down your kind of local alarm system. So that everything is peaceful there. And then the other thing is that they have incredible molecules
that block itch and pain. You don't feel it. And so one of the things
we're really interested in is can we follow these different things. And ask what is critical
for the pathogen to transmit 'cause you can imagine all
these things could really help. If you're a pathogen that's
trying to slip through the detection of the host. If all these things are
shutdown you really have an advantage in that process. So number one is
understanding what's important for the pathogen. And then number two is could
we just learn something about skin physiology and itch and pain by following these different molecules? We kind of think of them
as probes that we can go. Just crumbs that are
left behind to see how the tick has hacked into our system. Clearly the tick has evolved
to do this so effectively. It probably understands
aspects of our own body that we don't even understand yet. So we're trying to hitch
a ride just like Borrelia by understanding what the tick is doing to block all of those. So I think I already
mentioned all these points. Yeah and I just want to
emphasize how much saliva there is that's secreted. Over 90% of the blood meal
is condensed of the fluid of the blood meal is pushed back out. So what it's doing is
actually condensing down the blood proteins in its meal. And then the water goes back out which is what the saliva is made of. So you can cut a fed tick in half. I don't know if anyone's done that. Okay, just me. (laughing) If you cut it in half it's a little more like a jelly kind of consistency. Rather than, I was expecting. I was ready for like a water
balloon popping effect. So I had on like my goggles
and prepared for it. But it's actually more
of a gel like substance because most of the water comes back out. So that gives ticks a lot
of food for sustenance over potentially a long period of time. I think there's ticks
that have been documented to be out in the wild for years and have been able to survive that. And so they can take
in a lot of blood meal. In fact, I mean they
really take in so much that in some cases they can grow 500 times their weight through a single blood meal. Which is wild if you can imagine. Try and imagine that scale in yourself. And so here's a picture of some ticks that we have in the lab. What we have here on the left is a nymph and it's kind of the
size of, I don't know. Like a large course black pepper. And after it feeds this
is what we call engorged when it's completely done
feeding and falls off and it looks like this. And so it stays about
the same kind of length, width, size. And eventually molts into
this lovely female adult. And then this engorges in to this which is about the size
of a peanut kernel. And so they are really regulating us in order to complete this cycle. So I just wanted to. I know it's gross but
hopefully you'll remember it and think about tick saliva and. (laughing) And this concept of saliva
activated transmission. - [Man] Question, in the engorged tick. Is there any Borrelia
burgdoferi left in there? - Yeah, so the question
is in the engorged tick is there any Borrelia
burgdoferi left in there? And yes there it, yeah. Not all of Borrelia makes
it into the salivary glands. It can subsist across a molt. And that's also something
that's really different between the non-vector species and Ixodes. Is that the non-vector species
are good at clearing it and it doesn't usually
survive a translatial molt. So yeah, they can continue
to be carriers across more than one life stage,
the nymph and adult. And so one of the things
that we're doing towards this effort to identify salivary
molecules of importance. Is to start really collecting tick spit and looking at what's happening
in the tick spit over time in terms of what molecules are there. And I think you may have
noticed that I've mentioned a lot of different phases that
are happening during feeding. There's sort of the bite building phase. There's the slow feeding and
then they really ramp it up and start fast feeding
and then they detach. And saliva changes in its composition across each of those different phases to help accommodate those
changing needs of the tick. And so we're starting to collect saliva from different points. And I just wanted to show
you kind of how we do that. What we see here is a
partially engorged tick that we've pulled off the mouse. And we've literally just used Scotch tape and taped it down in the lab. A lot of what we do is just
kind of try to figure out how to do things for the first time. So yeah Scotch tape,
glamorous Scotch tape. And then we broke this thin
glass capillary needle or two. And you basically push it onto
the feeding organ of the tick and capillary action will
pull the water of it out which is the saliva. And there's a chemical called pilocarpine that will induce the tick
to salivate even more. And we leave them in this
little box overnight with this. And I don't know if you can see from there but the saliva's pulled
out all the way to here. And so we can collect saliva from ticks at different time points. And use tools to characterize
the different proteins that are in it. Look at how that changes over time and we're systematically
going through to see what these different proteins are doing. And then what's down the line is seeing if we can block it through experiments where we develop antibodies against them. Whether that could also block
transmission of the pathogen. Okay, so I think I
mentioned those as well. There's many more proteins
in the saliva of the tick. And so that is probably also
why they're such good vectors and very dangerous for us. So that concludes the different
topics I wanted to survey. I wanted to leave plenty
of time for questions 'cause I'm sure there's questions. So I'll go ahead and
open it up if you have anything you'd like to ask
that we can talk about more. Yeah, absolutely. So the gentleman asked the
other activities in the saliva like antibacterials and
anti itch, et cetera. Yes, there's a lot of interest in that. One group of people
that I didn't anticipate but makes total sense are
people in the catheter industry. Because a catheter is,
one of the challenges with catheters is they
have to remain in you for an extended period of
time, just like the tick. And they can get infected. There can be weird reactions
that are happening around it because it's a mechanical wound. And so they're very
interested in some of those exact properties in tick
saliva that could be used. We in my lab are currently
studying antibacterial enzyme looking at all the
different bacteria it blocks and it's really effective. So we're excited to figure out
how that potentially be used. And then we're also working with the lab. I think there are many labs
who are starting to partner with other labs. Like dermatology labs
or itch and pain labs. We have Allen Bossbaum here. His group studies itch
and we started looking at the ability of tick saliva
to block mouse itch. So what they do is this
really cool experiment where they can take mice and
video their scratching behavior in response to some
provoking with histamine or some other, something else. And then they can record
mouses scratching. And what we see is if we prime
the mice with tick saliva we see a reduction in that scratching. And other groups have seen
similar phenomenon in the past. So we're starting to
really mine if there's anything in there that can be used. 'Cause there's very few options
out there for itch and pain. Yeah, you know deet isn't
that effective against ticks. That's really more geared
towards mosquitoes, flying insects. Clothing is probably the best
external measure you could do. I mean I know when my
group goes out to actually collect ticks and we're really going out into the battle field. What we'll do is we'll
wear light clothing. Long sleeves and long pants
so that you can actually see but checking each other
for it is really important. But sometimes you know,
they just slip though. So we would always take, we always take hot showers soon after. That can deter a lot of the attachment. And then just paying attention after. It's challenging. They're determined to attach. Oh okay, so she's asking if
Borrelia is positively confirmed in your blood? What does that mean if
you're asymptomatic? It means you're infected and you should probably take antibiotics
to clear the infection. It means that you could
develop symptoms later. So I would take that seriously. Even if you don't have symptoms yet. Lyme disease is sort of notoriously known for having delayed onset of symptoms. Yeah, I think that's a really frustrating aspect of the disease for patients. It's hard for me to put a number on that and I think what we. I can only tell you what
we know which is that patients are clearly
suffering, they have something. And there's at least two possibilities. One is that it's in them
but it's hard to detect. The other is that it
could be something else. And so a negative answer
is the worst answer, especially for a test that's bad. So it's that absence
of facts and knowledge that's contributing to a lot of the maybe what you see that
seems sort of inaccurate or over blown out in the press. But I think what we know is that at least whatever people are suffering
from isn't over blown. But we don't know exactly what's going on and it's probably different in every case. And the concern about
infections with other pathogens is also very concerning. It could be that even if
someone has Lyme pathogen it's unclear if there could
be another pathogen there that's really making it worse or, yeah. So it's a challenging field. Yeah so, yeah. We can grow them in the lab
but you're absolutely right. He's asking if you can
sort of promote culturing of this bug in the lab
by giving it saliva? So, we have had a lot of
challenges growing it. But what people have done is not saliva but try to mimic things that
are happening in the blood. So the media we use which
is actually really expensive because we have to supplement
it with all kinds of stuff that you might find in the blood. We have to add gelatin to
make it a little more viscus. I mean it's such a diva. We feel like we have to do everything. Play the right music,
have the right attitude. Just like make sure every time it'll grow. But yeah, that's currently
the technology is to try and mimic the blood like environment. But it does beg the question, you know. We study Borrelia in culture,
in this specific culture. But it cycles between totally
different environments. The tick, the human, blood, tissues. Even within the tick the
salivary glands in the gut are so different. So there is a push in the field to try and figure out if there's ways to study it in these more natural environments. Because it clearly can adapt
and have a totally different physiology as it's moving throughout. So some of the culturing
methods could be biasing us towards a specific condition, yeah. Yeah, that's a really good point. So there is an antibody response to. Well, there's an antibody
response to some things in a tick as well. But there's also an antibody
response to some of the proteins that decorate the
surface of the bacterium. So that's classically
what's been looked at and also what the vaccine
was developed against. It has a lot of different
proteins on its surface. And that coat of proteins
kind of changes also while it cycles between
the different hosts. So that's been a very
active area of study. What Charles Choo is doing is looking even more broadly than that. That was sort of more
of a candidate approach but he's looking just
sequencing the entire response. I think he would have to tell you more about what they're finding there. Yeah, that's a great question. That really hits at the heart
of some of the challenges. So she asked whether the
symptoms that you have in response to the pathogen
are your immune system over reacting to something
and going into disarray? Or if it's the actual
pathogen doing something. And I think the answer
to that is it's likely a combination of both to varying degrees depending on the patient and the case. But that is an active
area of study for sure. Just seeing if it's like accidentally over activated some aspect
of immune system that. One thought in the field by some is that even if Borrelia has been cleared. It's really the scars of
that on you immune system are still at play. And could that be
contributing to some of the long term effects? But it's not totally clear. That's a really hard one to ask. It's not like another
pathogen where you can very clearly say what the contribution is. Oh yes, definitely. So she asked another sort
of knob we can turn on is walking the reservoir animals that are the original
source of the bacterium. And so there are definitely groups, especially on the east coast
who are thinking about this. How they can play around with the ecology of the actual animals
that the ticks feed on. I think there was an article
about it in the New Yorker a few years ago. This guy out on the east coast
who's trying to play around with the animal population. I think near Long Island,
I'm not totally sure if I'm getting that right. But yeah, and then I think
there were even efforts at one point of trying to
deal with some of the deer. I'm not sure if they ever did this but it was one of the
ideas of trying to control the deer population by suggesting that deer hunters on the east coast try and focus their hunting efforts to deer near residential areas. But you could imagine encouraging hunting near residence is maybe
not the most strategic way to go about it. But if you're just focused on the ticks you may not realize that at first. So yeah, there's been
a number of discussions around that too. I mean I ultimately think
that there's not gonna be a single silver bullet. That probably it's a
combination of everything from education, ecology, you know to medicines. So she's asking what
are the risks associated with city dwelling ticks? And their hosts that are
more in the city limits. So I think one of the
problems is that we are moving into forested
regions more and more right. So that's one of the
things that's contributing to the expansion of Lyme disease is that areas that were previously forested and not occupied by
humans we're moving into. And it's that collision of
those ecological systems that's causing this problem. So I think that's just
one part of the answer. Some regions on the
east coast in particular when you see more people
expanding that perimeter of what city you see more of that. But there are other things in the city. Tularemia is a less common
disease that's caused by ticks. But it's caused by ticks
that feed on rabbits. It's also know as the lawnmowers disease. You mentioning the lawnmower
made me remember that. But it can be transmitted
both through the tick and through breathing of this bacterium that's carried by rabbits. And so there's been cases where
people mowed over a rabbit or something and were infected with this. But ticks can carry that
for example as well. So there are other things out there besides just Lyme disease. Especially here on the west coast and I think that's one of the reasons the Citizen Science
Project is so important. 'Cause we can start getting some of that granular information about
what people are running into in urban areas or in forested areas. Yeah sure, it is. Because climate change is gonna effect the animal population. And so if you have an
expansion the animal population we're seeing an uptick in ticks, we're seeing an uptick yeah. (laughing) There was, I had a few years ago. I can't remember how many years. Goes by so fast. But you know, an example of this was that there was like an acorn
bloom on the east coast which turned into rodent
bloom in response. Which turned into a tick bloom later. And so there can be a lot of sort of trickle down effects from global warming. It's wild, I only started doing. I've been doing this for a couple of years but what I've been hearing
from a lot of people is that they're seeing
more and more ticks. People have lived here
for a very long time. Right now we're really focused
on China Camp State Park. We did a bunch of kind of
small surveys here and there. There's actually somewhere near Monterey called Garrapata State Park
which is Spanish for tick. So not surprising that
we found stuff there. But the reason we decided on China Camp is people are running into ticks a lot. And they're running into ticks that a small percentage are
infected with Borrelia. The other reason we thought
it would be useful to focus in and do a longitudinal study in one region. Is that area could correlate
with a lot clinical data from Marin General. And so we're hoping to see if we can identify things in the ticks. But also have sort of a reference
point to cross reference and see if we're finding
things that people are actually getting infected with. So that's where we are right
now but there's, I mean. There's way more than just
my group looking at this. We're a small piece of that puzzle. There's a lot of different
agencies that are tracking different areas
that you could easily look up some of these agencies and see what they're monitoring, yeah. Okay, great. Thank you so much. (applauding) (casual music)
