So I wanted to start my talk with asking a question.
What if you could look inside your body
to the most minuscule detail?
What if you could look at your individual cells?
And better yet, what if you could actually look inside
those cells? And see the inner workings that make up
the life of that cell.
What if you could actually read your DNA sequence
and understand what is that DNA sequence telling you?
What is the program that's encoded in that DNA sequence?
This is the science of structural biology. 
It's a visual science,
where we try to look at the most minute details of life
and try to understand how life works.
And also in disease states,
how things are going wrong within those cellular structures.
And then, in pharmaceutical industry for example,
how can we intercept those diseased cells
or tissues to correct the disease state.
All this requires visualising and understanding
to the most minute detail of the life that you're studying. 
So with myself, I got into this field... In high school,
I knew I wanted to be a scientist.
I was very analytical, logical.
I wanted to understand things, understand the natural world.
But, I couldn't decide between biology and chemistry.
So I progressed in my studies. And in undergraduate studies,
I discovered biochemistry,
which is combining those 2 fields.
But it was also very fundamental science.
It's the fundamental science behind
molecular biology, immunology, botany,
everything that we've heard today from other biologists,
where life can be reduced to chemical reactions
and interactions between different components within cells.
So one life changing moment for me was when,
in my 2nd year of undergraduate studies,
a professor took me on
and a small group of other undergrads
who really didn't know what we were doing.
We're just beginning our careers. But he trusted us
and giving us research questions to address,
and to do our own independent research,
and come back once a week and discuss as a group.
And, it was really ground-breaking for me because 
I looked at professors with awe -
these people were experts in their field.
They’ve been doing this for decades
and here I was, a lowly undergrad.
And this professor was trusting us with helping him
with his research. That was one life changing moment.
A 2nd life changing series of moments was:
I've always been interested in
the history and development of science.
The philosophy and how scientists should think
and how the scientific method operates. 
So one of my favourite authors growing up was
reading Carl Sagan. So he's an astronomer.
Unfortunately, he's not with us anymore.
And he is an amazing science communicator.
So if you're interested in science communication,
look him up.
He had a documentary series on astronomy in the 1970s
that was beautiful. And now, it's actually been
recapitulate and reinvented by Neil deGrasse Tyson,
and it's been awesome as well.
So, just what Carl Sagan communicated in his words
and his program was just: how crazy beautiful the world is,
the universe is. So some of us manifest that in astronomy:
we try to understand how the universe works.
But to him, it was almost a spiritual journey, where
it's almost a religious experience just to understand how
crazy complicated the world is. So for me,
I applied this through understanding the minute details of
life in biochemistry.
So structural biology teaches us that biology is arranged
around this axiom that form equals function,
or determines function. So what I mean by that is that
the arrangement in 3 dimensions of
an organ, a tissue, an animal,
or even down to the most minute structure of life, DNA.
The arrangement in space determines what that thing can do.
So, you might be familiar with the structure of DNA
as a double helix.
It's that way because that structure provides it with
2 functions. It can copy itself. It has 2 strands.
They can separate and then become the copy of themselves.
And also, it encodes information to create proteins.
And this is where people don't really...
Maybe, if you're not familiar with biological sciences,
proteins are this black box.
But proteins are the workhorses of life.
And this is really where this concept
of form = function 
plays a really, really important role.
So that's actually what I'm showing here
is a variety of protein structures,
3D structures that have been determined
by scientists over decades. And to me, these are amazing!
You're looking at the most fundamental details
that create life,
that catalyse chemical reactions,
that create particles that infect other cells.
And every time I see these, it's an amazing experience.
And I've looked at hundreds of these over my career.
But every time I discover a new protein structure,
it's another amazing experience.
So for example, this is a virus.
This is actually only about 1 or 2 or 3 proteins that
form this outer structure of the virus.
So this blue coloured is almost like a soccer ball.
They’re individual proteins that touch themselves and
form this, like a soccer ball, structure
that forms the outside of the virus
and the DNA of the virus is inside.
Another cool structure is this.
This is called the chaperone.
And this is a series of proteins that forms a cage,
sort of like a virus but this is with a different purpose,
where proteins inside
can assemble themselves as they need to.
So it's a chaperone, meaning it helps other proteins
adopt the 3D structure they need to do their work.
Another protein I wanted to show you is over here.
This is called myosin.
This is a very important protein found in muscle cells.
This protein can expand and contract,
and utilise energy to do so.
And as we know, this is what muscles are supposed to do.
So muscle cells are able to expand and contract,
and this is due to the function of the myosin protein.
So in my work,
I'm interested in discovering new protein structures.
So specifically - I have various research interests -
but today for the sake of time,
I’m telling you about 1 of my main research interests
is antimicrobial resistance or antibiotic resistance.
So this is the superbug phenomenon,
where bacteria are able to cause infection in humans
and they're very, very difficult and increasingly impossible
to treat with antibiotics.
So what are antibiotics?
These are basically wonder drugs
that were discovered in the earliest 20th century,
starting with penicillin.
Where previously infections caused by bacteria
that would kill you
and have killed millions of people over civilization:
cholera, the plague, diarrhoea,
even sexually transmitted diseases caused by bacteria
could be cured by these miracle drugs. called antibiotics.
So of course as humans often do,
we became irresponsible with them
throughout the 20th and now the 21st century.
We use antibiotics when we shouldn't be using them.
We overuse them in medicine.
Probably many of you have gone to a doctor
and then diagnosed with just a flu, a cold -
chances are it's caused by a virus.
Antibiotics don’t work on viruses,
but maybe the doctor prescribed you a course of antibiotics.
So what those antibiotics do is create this huge pressure
on the bacteria in your system to fight back.
And this is actually where bacteria are winning this battle.
So bacteria are amazing at adapting.
And they've seen, as we heard with George's talk,
they can exist in crazy environments
- like at the surface of volcanoes.
So bacteria have seen all these stresses
throughout the eons that they've been around.
And they've actually seen antibiotics before as well.
So this huge stress. So in medicine, we overuse antibiotics
and in agriculture as well.
We add antibiotics in farm feed
to make chickens grow fatter, pigs grow fatter.
But they're not sick. We just add them
because the industry thinks
or they've been conditioned to think that
this enhances the production of the animal.
So this is creating this huge pressure on 
bacteria to fight back and of course they do.
And what do they do? They evolve these proteins,
molecular machines - we also call them.
They've evolved proteins
that are able to sense those antibiotics and destroy them.
They've evolved proteins that are able to
enhance the structure of the bacteria to make them
more impenetrable to the antibiotic.
Or they've evolved other proteins that
find the antibiotic that's inside the centre of the bacteria
and spit it out.
So in my work, I'm trying to understand how is it
that these bacteria are able to evolve
these molecular machines, these proteins are able to
resist antibiotics.
So then using structure biology techniques,
I've been able to discover brand new ways
that bacteria are able to do this.
And then, we've been working with pharmaceutical companies
that then take our information from these techniques
to then improve that chemical structure of the antibiotic.
So maybe the bacteria can't identify and destroy it anymore.
So this is a really important field.
And, we're fighting back against the bacteria.
But it's an endless, it’s going to be
an arms race that will continue for decades.
And we hope to not return to that time,
when we didn't have antibiotics.
And we had these plagues and really serious outbreaks.
So hopefully we won't get back to that time.
So that's a little bit of what I do and
I hope I've given you a sense of what structure biology is
and how it's a fundamental science that
really drills down to the inner workings of life itself.
And I hope I've given you a little bit of a sense of
what inspired me to get into this field.
But I want to leave you with 1 message.
We've learned a lot about different sciences today.
And I think the unifying principle behind
how we've been able to have these careers and learn
things about the world is the method of science itself.
And it really is the best method we have,
as a civilization to address
serious problems that are facing us:
climate change, overpopulation, sustainability issues,
resource utilisation. That template of being critical,
analytical, developing a theory, testing the theory,
and maybe throwing it out -
if your observations don't accord to that theory -
and iterating that,
and progressively finding more and more information.
We can actually apply that to all walks of life.
So whether you're in law, whether you're in history,
whether you're in philosophy, whether you're in art
that template of being critical, developing a theory,
testing it and maybe changing your theory
to come up with a better one.
I think serves us well as a civilization.
So, thanks!
- What is your favourite
or the most interesting superbug you've worked on?
- So there's... It gets pretty scary.
So there's some bacteria that...
There's a bacteria, called Acineto baumannii,
and it's found in the Middle East. So a lot of
war veterans that have come out of Iraq war for example,
US soldiers, have gotten sick with this bacteria.
And it's resistant to basically every antibiotic we have.
There's about 20 or 25 different classes of antibiotics.
And this bacteria can resist all of them.
So we're trying to understand
what makes this bacteria able to do that?
What are those molecular machines, these proteins that are
able to do that?
And we're trying to improve the antibiotics we have
that might give us an extra window of time,
in which we can treat these serious infections.
But people are dying from these bugs
and it's increasingly a more important problem.
- So these bacteria are presumably evolving their resistance
blindly through natural selection.
Is there a way to have the proteins
undergo natural selection to
just blindly evolve ways to kill the bacteria?
- Well, it's not the proteins that are killing bacteria.
It's the chemicals themselves.
Yeah, so I mean that's, I'm sure,
I hope pharmaceutical industry is doing that:
where you can actually...
So, actually that's routine now
is that when a new antibiotic is being discovered
or developed, they immediately look for resistance
because you know it’s going to happen.
And then, you sequence the genome of that bacteria
and you discover what is the protein that confers that
resistance, and then you feed that back into your chemical
synthesis that makes the antibiotic.
So it's almost like... Now is considered that
antibiotic resistance is inevitable.
And because of this natural selection and
that's being fed into the drug development pipeline.
The only problem is it's expensive and takes a lot of time
to develop any of these drugs.
And unfortunately, a lot of pharmaceutical companies
don't do it anymore because they can't make money off it.
So that's why academic scientists are doing this.
So we're trying to take that evolutionary approach,
where we know resistance is going to happen and
we incorporate that as much as we can into the chemistry
of the antibiotics themselves.
- So you were mentioning an arms race and
how the bacteria are getting better
and then we get better antibiotics, and etc. etc.
But in biology, we know that the best relationships
between multiple species are symbiotic ones:
win-win situations.
So you develop in concert
and you both give each other a hand, and then
everything's hunky-dory.
So, is there much research into these multi-community
approaches to bacteria that,
instead of treating with antibiotics,
let's treat with other biotics
that can then create more of a balance?
- Yeah, absolutely. No, that's a huge area of research,
where the industry and scientists in academia as well
are realising "You know what:
maybe antibiotics are not the way to go".
Even if we do invent a new antibiotic, within years,
it will go obsolete so to speak.
So yeah, there's a lot of research going into
understanding the community.
So basically when we take an antibiotic,
it's going to be destroying
the communities of bacteria that are naturally within us.
And it's putting things out of equilibrium.
So yes, absolutely people are looking at:
what are the species that need to exist that would keep
the pathogenic species on check?
So it's not my field of research, but definitely it is.
So we were talking before the talk started actually that
C. diff is a bacteria that people get infected with that
in hospitals. And a cure - it's a little bit gross.
But a cure is replenishing the natural microbiome
in your stomach, which is basically other bacterial species,
from poop.
So people are developing ways to
maybe make this more amenable as a drug.
Because we don't want to be eating poop.
But basically, poop is a collection of bacteria,
a community of bacteria so to speak that
has come out of you. So we know that cures this.
We know that cures C. diff infections
- better than any antibiotic.
So people are researching new ways to harness
the beneficial bacteria from poop, or maybe some other way,
and then putting it back into your system.
And then those beneficial bacteria will take care of
the pathogenic, the bad ones.
So yes, absolutely that is burgeoning research for sure.
- I'm so glad somebody brought it back to the whole saliva,
spit thing, because we have to remember
that "you are what you eat, minus what you excrete".
And we're actually losing our microbiomes.
And this is actually a huge issue
that we don't have that diversity.
And there's amazing, I'm sure you know about it
in your research, showing that because
our microbiomes change, we're actually...
Our whole interaction with food and nutrition,
and our immune systems is a super...
I just read this amazing article in The Atlantic.
Anyway, you probably saw it.
- No, it's not my field. I’m not into microbiomes.
But it's crazy! People think that a lot of diseases:
Alzheimer's disease, even psychiatric diseases
have to do with what bacteria are existing in our gut,
intestine, stomach etc. It’s not my field,
but it's pretty crazy stuff
where there's this gut-brain axis and
we don't fully understand it yet.
- Thank you so much, Peter!
