>> Okay, welcome back.

Quick sound check.

Everything okay?

Great, thank you.

Welcome back.

Today, we're going to be finishing up the topic

that we were talking about last time.

Last time, we were talking about combinatorial approaches

in chemistry and then we'll talk a little bit more

about combinatorial approaches in biology.

And I'll show you a couple of examples of this.

All right.

Okay, that's interesting.

All right.

Okay, so again we're here.

We just completed our survey of biomolecules.

I'm going to complete the topic of making combinations

of biomolecules and then we'll talk

about tools for chemical biology.

And this is really important because these are the tools

that you're going to be using when you write your proposals.

So I'm glad you're all here today

because you absolutely need to hear this to be able

to write a good chemical biology proposal which recall last time,

I told you was going to substitute

for the final exam in this class.

There is no final exam in this class.

We will not have a final.

Instead on the very last day of class,

you will hand me a 10-page or so proposal, a written proposal

with figures and it'll be an original idea,

something that no one in the planet has thought of before.

You will be the first.

And it's going to be really fun because it's really great

to come up with creative ideas

and that's really the ultimate goal of science.

Science is really a creative enterprise.

Our goals are to invent new concepts,

to tell people new visions of the universe and to do this;

we have to somehow invent these new experiments to do.

Okay, so I'm going to be talking to you today about the tools

in your toolkit that you're going to be using

to do this assignment.

Okay, I already talked about these announcements.

I'm skipping some stuff.

Oh, office hours.

I had office hours yesterday that got derailed

by a student emergency and I know at least one

of you sent me an email about that.

I apologize.

I will have office hours today and in addition,

I sent an email back to that student.

So I apologize if you came by yesterday.

There was a student health emergency

that absolutely needed my attention and so I had

to close my door to deal with that.

Okay, so apologies there.

Other office hours, tomorrow, Mariam will have her office hour

on Friday and I'm hoping Kritika will be back next week

and I'll introduce you to her

and she'll have office hours next Tuesday.

Okay, so all right, any questions about any

of the announcements, things like that,

things that we talked about last time?

Questions about the course structure?

Oh, I got an email from someone

and I apologize for not replying.

The email was, "When are you going to post online the slides

that I'm flicking through?"

And the answer is I'm going to try to get to that today.

And then my plan is to basically post all of my slides

from the previous year and so that way,

then at least you'll have a guideline

for what the slides will look like.

Chances are, I'll heavily modify these

or slightly modify these depending

on how much time I have before each lecture.

I mean, literally five minutes before the lecture,

I was making changes to the slides.

It's almost impossible to stop me from doing that.

I just love this too much.

So because of that, I'll be posting kind of a guideline

for what the slides will look like in advance.

And then I'll come back

with something that's more definitive.

Okay, so at the end of today's lecture, then I'll post all

of the week one slides in a definitive way

but I'm also going to post last year's week two,

week three, week four, et cetera.

Okay, sound good?

Okay, any questions about that?

Okay, great.

Okay so let me review what we talked about last time.

If there are no questions about any announcements or things

like that, we're going to go straight into the material.

Okay, good.

So what we talked about last time was the definition

of chemical biology.

Chemical biology uses techniques from chemistry,

often new techniques from chemistry, often techniques

that had been invented specifically to answer problems

of biology but not always.

And then these techniques from chemistry are used

to address understanding biological systems

at the level of atoms and bonds.

That's the goal of chemical biology,

to really understand how organisms are living,

how they do the things they do at the level of atoms and bonds.

Okay, so I'm really fascinated to know

about that hydroxide functional grid

that donates a key hydrogen bond or provides a key Bronsted acid

to some mechanism in an enzyme-active site.

That's the part that makes run to work,

the sort of the details of this.

I basically want to use the arrow pushing that you learned

in sophomore organic chemistry to explain biology

and that's the goal of this class

and that's the definition of chemical biology.

So last time, we learned about two key principles

that organized biology.

The first of these is essential dogma which provides the roadmap

for all biosynthesis taking place inside the cell.

Everything that the cell has to synthesize will flow

through this central dogma.

This is the flow of information for biosynthesis by the cell.

So everything that your cells will synthesize is going

to be encoded in some way by the DNA inside your cells.

Oh, and can I ask you if you have an empty seat next to you

to move over to the right just to open

up some seats on the edges.

Some people I know are coming in from other classes so you know,

so other classes that are ending

about when our class is starting.

So if you have an empty seat on your right,

if you can just scooch over and leave seats on the edge,

that would be really appreciated.

Okay, thank you.

Okay, so the second key principle

that we discussed was evolution.

Evolution provides a principle

that helps us organize vast amounts of knowledge and really

in the end simplifies biology enormously.

And it's actually a principle that all of you are going

to be applying when you design your chemical

biology experiments.

Because I will tell you in advance

that I will not accept any proposals

that involve experiments on humans, okay?

So experimenting on humans has its own special topic

that I can actually teach a whole quarter on.

Okay, it requires ethical considerations.

It requires tremendous design considerations.

It's not nontrivial to sample, for example,

a diverse population of humans and ensure

that you're getting diversity.

So all of those considerations are beyond the realm

of this class.

So instead, what I'm going to ask you to do is experiment

on non-human organisms.

You might for example choose cells from humans

or you might choose model organisms.

And by choosing those model organisms,

you're applying a key principle from evolution which is

that that model organism descended

from some common ancestor that we share and in doing so,

acquired the same mechanisms that govern its chemistry

and its chemical biology.

And so that means, if we learn something

about this model organism, we can then apply that knowledge

to understanding how humans work.

Now naturally, there's limits to this, right?

If your model organism is a salamander and you're interested

in understanding how the salamander regenerates its arms

when you cut them off,

which incidentally would be an absolutely fascinating topic

for a proposal, right?

There's a limit to how much analogy you can do back

to humans, right?

We humans don't have that same mechanism obviously

and it would be absolutely fascinating for me to learn

from you how it is that you plan to apply the biochemistry

that you are learning about stem cell growth

to develop say limb regeneration in humans.

I would love to learn that.

Okay, so evolution is important to us because it tells us

that fundamental processes are more or less the same

for every organism on the planet.

And I'll be showing you a few examples in the next few weeks

that illustrate this universality

of chemical mechanisms.

In addition, we also saw that evolution is really a tool

by which we can evolve molecules to do powerful stuff

for us inside the laboratory and I want to pick

that topic up for us today.

Okay, so I'm going to start there.

Any questions about anything that we saw on Tuesday?

Okay, now I also got some really fascinating emails

from some virologist in the audience who pointed

out there's actually the coronavirus protein

that is known to start with an RNA template

and then replicate RNA and that's absolutely fascinating.

I wasn't aware of that.

So there are exceptions to what I'm teaching you.

I'm going to try to teach you the sort of most general thing

and yes, there will be exceptions.

Don't hesitate to point them out to me.

I'm fascinated by those exceptions too.

Okay, so let's pick up where -- okay, before we do, last thought

about this proposal assignment.

To do the proposal successfully, what you have to do is you have

to come up with a novel idea, okay.

I will not accept any proposals

that don't have something new in them, okay?

And I will actually ask the TA's to do Google searches

and literature searches in PubMed and other sources

to verify that what you're proposing

to do has not been done before, okay?

So you have to come up with a creative new idea.

This sounds daunting but let me provide some guidelines

on how to do this, okay.

So the first thing that you need are a series

of experimental tools and then knowledge of the problem.

Okay, so experimental tools, I'm going to provide to you today.

I'm going to give you a toolkit by which you can go out

and start to address problems in chemical biology.

The second portion, knowledge of the problem.

You need to know that actually, you know, there's a key step

in limb regeneration that's not so well understood.

That second step comes from reading the literature, okay?

And the first assignment in this class,

the journal article report is designed

to help you address this second thing,

knowledge of problems, okay.

So in doing the assignments that are required for the class,

these two things are going to come together, okay.

Today, we're going to address number one

and then item number two, you're going to get by Valentine's Day,

February 14th, you'll have a journal article report and then

in doing this assignment, you'll be looking at the literature

and you'll start to identify problems in the field

that interests you, okay.

So you'll choose a journal article that's relevant

to your interest.

I don't know what your interests are.

Let's say you want to be a dermatologist, okay.