1. Introduction, Course Organization of MIT 7.016 Introductory Biology, Fall 2018

BARBARA IMPERIALI: OK. We're going to get going. Now, we have a small
class this year because of changes in the
institute with pass/fail types of things, but Professor
Martin and Dr. Ray and I consider this to be a
special opportunity for us to run the course a little bit
differently with a few more quirks and surprises. Because we have a
small number of you, we can listen to you all. We can get input from you. We can even get feedback
from you of something you might like to see more of.

And in general, we really want
to capture the sense of you. I have looked at the
registration list. We have people from every year. We have people from many,
many different disciplines. So this is what we're going to
do today after we I start doing some introductions and so on. We're going to talk
about the nitty gritty of the organization. We need to tell you this. We need to convey this
information to you clearly about when exams are,
and what requirements are, and how to do well in this
course without even realizing it, that kind of thing. And then I'll take you through
this sort of fast track through molecules to
man, all the way down to cells and
organisms, to show you that there was a breakpoint
in the 1950s where the structure, the
non-covalent structure of DNA was elucidated.

And there was an
entire revolution after that which makes
modern biology, the study of modern biology, so entirely
different from the study of biology in the
era before that. Biology used to be considered
taxonomy and dissection, like listing and looking at. But now biology, modern
biology, is a molecular science. So as we talk about these
topics, what you will see is the blueprints for life are
common across domains of life. And if you learn
basic principles, you'll have an exponential
increase in your ability to appreciate these
characteristics, that modern biology is
a synthesis of science, technology, engineering,
where all the tools from those disciplines, different
disciplines– physics, math, computation– funnel into modern biology to
make what we know now feasible, and that's a dramatic and
fantastic opportunity for all of you moving forward
in your careers.

Now I want to
introduce the team. So I'm Barbara Imperiali. I'm a faculty member in
chemistry and biology, and I'm really interested
in chemical biology, glycobiology, biophysics. I love to tease apart
complex pathways in organisms where you biosynthesize very
unusual glycol conjugate that are very important for cell-cell
communication and host cell pathogen communication,
for example.

I was trained as
an organic chemist. In fact, I did my
PhD degree at MIT about five million years ago
on a sort of current scale. So my co-instructor
is professot– sorry about this, but
they want us on video. ADAM MARTIN: Hello. I'm Professor
Martin, and my lab is interested in how cells
generate mechanical forces and how this is involved
in sculpting tissues during development. BARBARA IMPERIALI: So what
Adam hasn't told you is he's a cell biologist,
a biophysicist, and he's a lot better
at genetics than I am. Our instructor is Dr. Diviya
Ray who's been with this course, now this is the
sixth year, and she is trained in immunology,
cancer biology, and also cellular signaling. But what you can't
tell from that is how dedicated she is to
each and every one of you. If you have any trouble in the
semester, just contact Dr. Ray and say, I need some help,
be it a particular problem in the material, or there's
just something come up that makes it difficult for you
to do your best in the course. She will help you.

She'll work out mechanisms to
get you through troubled spots. So let's get going here. Now, what I want to
try to do is just give you sort of a
flavor of where we're going to within the course
by starting with a few bullet points and topics just
that I can sort of pique your interest. So as I mentioned
before, studying biology in the 21st century is
a fabulous opportunity. No matter what
discipline you come from, you can add to the expertise
that will move biology forward. Biology would not
be where it is today in the absence of science,
engineering to promote it and to support
progress in biology. So you really want
to realize that, that you have an opportunity.

You may say, well, I'm in
this discipline or other. I don't think biology is
going to have anything to do with my future career
or career opportunities. But it has a lot to
do with your life. It has a lot to do with
understanding health and disease, understanding
new scientific discoveries and developments. So it's so important
that you, as a scholar of the 21st century, have a
good grasp on these materials.

And we're not trying to feed
you anything dull and boring. This is really exciting stuff,
because the level of complexity that we can study nowadays– whole genomes, whole organisms
at a molecular level– is amazing. It's amazing. We're not just
peering down a slide and looking at one
cell or something. We will be able to
do full descriptions. So what we'll try to
give you is a view of the fundamental
principles that are common to all living organisms. So the study of
biology, some people are microbiologists, or
eukaryotic biologists, or human biologists,
or they study virology. But we're going to build for
you, in the first few weeks of class, information on
the common building blocks that go across all
domains of life. Because once you start to
learn about those molecules, the build up, the
macromolecules of life, then you'll start to really gain
an understanding how amazing it is that these same
sets of molecules function across from
bacteria to man. So you learn the rules for
the simplest organisms. You look at the
molecules and you see how form fulfills function,
which is something I'm really excited about,
and then you'll be able to apply it as we get
ever more complex systems which demand a lot of attention.

So there's a common
molecular logic of very complex processes. Motivations– I just
mentioned a few. Sure, you want to understand
health and disease. You want to understand
what might be going on with current therapies. When you have a relative
who's been diagnosed with a serious disease, what
are the current opportunities? What's coming down? What sorts of opportunities
for therapy might be available? Because there are
so many diseases now we understand at
a molecular level. We may not understand
how to treat them yet, but we understand
what their origin is, and that's why molecular
approaches are so important. You may often hear
of words like systems biology and synthetic biology. These are kind of jazzy words
for fairly straightforward things.

Systems biology is a
little bit like treating an organism or a cell as an
electrical network, a wiring diagram. What proteins talk
to what proteins? What are downstream functions? Where are signals amplified? And so on. So that's systems
biology at its heart, quantifying different
intermediates in a complex map of the cell. Synthetic biology is
about using biology to make stuff, which
is really cool. Many, many important molecules
can be made in the lab, but it's so much more effective
to make them in an organism. People are doing what they
call synthetic biology, and that's exploiting
and harnessing nature to make things that
are useful for mankind. And all the way
through, what I just want to emphasize how
integrating technology and engineering for
science is really what we're all about
here, because we appreciate we couldn't make
the progress without it.

There are also issues
general biology impacts that are in the social
sciences and impinge on things like ethics,
designer babies, cloning people, cloning your
pets, all kinds of things, treating a disease through
genetics or not, [INAUDIBLE] some of these new innovations. But you really
need to understand ethical issues
related to them to be able to explain to your
parents, or your grandparents, or your sister or brother who
hasn't taken biology, what the implications of
some of the things that we can do in
biology, but probably we shouldn't do in biology.

And we will welcome your
thoughts on some of that later on. OK. So where did the world start? Arguably four and a
half billion years ago is kind of a vague
theme, but it started with the world, the earth,
being a ball of fire, and it took quite a
while for it to cool down to establish the hydrosphere and
the globe as it's known today. There was a period of time known
as the prebiotic world, where there were not living
organisms that replicated, and that was basically a world
where building blocks started to evolve out of
fiery hot mud pits and in volcanoes and
goodness knows where.

People believe that
the building blocks of life, just the
molecules, came together from things like hydrogen
cyanide, or sulfide, or other primordial
components that were in the primordial soup. There was a phase known as the
pre-RNA world, where the RNA building blocks were around. There's reasonable arguments
in favor of the RNA world, where a lot of
functions were catalyzed not by proteins, but by
nucleic acids, specifically ribonucleic acids. So it's a period of
time still pre-biotic that had the first pre-RNA,
and then RNA world. But then things really
started to get interesting when the first cells evolved. Now, I will talk a little bit
about this in the next class, because the thing
that's critical to be able to build a cell is to be
able to build a wall around it.

So very, very early on in life
lipid bilayers, membranes, evolved in order to make
compartmentalized structures where you could differentiate
the in from the out. And so much of life is
completely reliant on the fact that we're made of cells. We're not just one big sort
of bucket of water with things floating around in it. Because so much of function
becomes coordinated by cellular compartmentalization
through things known as lipid bilayers, which
are semi-permeable membranes.

Oxygen can move across. Some small hydrophobic
things can move across. But a lot of things get
either stuck in or stuck out. So we'll talk a lot about that. So the first prokaryotes
were cyanobacteria. They're photosynthetic bacteria. It was quite a long time until
those unicellular organisms that totally lacked a nucleus,
lacked a lot of intracellular compartmentalization,
evolved to eukaryotes, and those cells are different. They're 100 or
1,000 times bigger. They're complex. They're compartmentalized. They can do a lot of functions. In a full organism they're
very differentiated, and they may look different
in muscle, or in heart, or in skin, or in bone. And so those eukaryotes– so
that's a long gap of time, but there was a lot
going on in that phase.

And about a half a billion
years ago, multicellular life evolved. And multicellular life
now can be looked at, if we think of the
evolution of homo sapiens, can be thought of as something
that we can keep track of a bit through fossil records over
the last five million years, where the first
humanoid life evolved. Then you got sort
of to a stage– I think he's homo ergaster, that
this sort of Shrek-like person evolved quite early on.

And then the humanoids gradually
became different, evolved. In some cases there were
branches of the tree of evolution and dead ends. In other places
there was a branch that carried on for a while. For example, the neanderthal
and homo sapiens kind of kept on evolving for a while. But there's a lot
of developments that have been characterized
from the fossil record. But now there's a lot of belief
that if we trace things back through genomes, we might
get more precise information on steps in evolution. Now, the evolution of the
advanced, if you will, hominids really came along
with a number of things. There was a stage at which a
particular gene, the FOXP gene, is attributed to the
ability for complex speech. And that could have been a
leap forward when humanoids could communicate
more, and it seems to be associated with that.

But there are other sort
of sociological functions, like burying the dead,
or making jewelry, or making tools, that are
associated with the more evolved organisms. There are other types of things
like cranial capacity, standing upright, looking forward. A lot of things came through
those years of the evolution of homo sapiens. So it's fascinating
to think about that and to think what light
genetics can shed on those five million years of evolution. Now, the world of biology
took a mega kick start with the elucidation
of the human genome, but more importantly
of the technology necessary to solve the map
of the whole human genome. In 2001 there was
a major development with the publication of the
first map of the human genome. It's fascinating to
think with humans, we humans have about
three billion genes, but there's only across human– is that right? No, sorry.

Base pairs, yes. Thank you very much. But across humankind
there's enormous diversity, but that's accounted for by only
about 0.1% of the diversity. So you can see people
look very, very different, but we still share
99.9% of our genome. Another very interesting thing
is that genomes vary in size quite considerably. Before I move
forward, I just want to quickly show you this map. I mentioned tracing evolution
through a molecular clock, so looking back in time not by
following the shape of a skull, for example, or
physiologic changes, but looking at genomes using
the genome as a molecular clock based on mutation rates that are
fairly constant amongst domains of life. You couldn't compare a
human and a bacterium, but you can go back through
a lot of eukaryotic evolution and see where
divergence has happened. So in this map, you can see that
human and neanderthal diverged from the chimpanzee
a certain time ago, which had diverged from the
gorilla further ago based on the molecular clock
that's available.

OK. So now I want to talk
a little bit more about getting into the
details of the genome. So genomes differ
greatly in size. Our genome includes about
three billion base pairs in our 22 chromosomes plus
the X and Y chromosome, but the typical genome
of a model bacterium has only five
million base pairs. So far, far smaller,
more tangible, more easy to study,
because those genes are more limited in
size, but the genome size is not necessarily
proportionate to the number of genes that are expressed
and made into proteins. A fascinating discovery is
that of the three billion base pairs, only about 1.5% to 2%
actually code for proteins, and there's a ton
of interest now in what's the rest of
the genome doing there. Where did it come from? What's its function? There are different
functions that Eric Lander calls the dark matter of the
genome, different functions to the rest of the genome. But the part that we
focus on is the part that gets encoded
into proteins that form the functions of
the molecules of life.

So we're going to focus
ourselves in on those. But here you see differences
in sizes of genomes based on base pair. But what's fascinating is
despite this huge breadth of sizes and huge
differences in organisms, the building blocks
are the same. And that's what I think is the
wonderful part of what we're able to teach you is, we
can take you from the 1950s when the structure of double
stranded DNA was first solved. Now, there were 60, 70,
or more years of work before that where they
figured out the pieces, they figured out the
chemistry, the covalent bonds, and the bases, and the sugars,
and the phosphodiester. But they had no clue how the
DNA could encode and program the synthesis of a protein. But once the structure, the
three-dimensional structure of double-stranded
DNA was solved– this is this beautiful
anti-parallel structure that you see here– by Watson, Crick, and
Rosalind Franklin, then the clues came pouring in. Without that structure, without
the structure of what's known as the non-covalent structure–
not the covalent structure, you'll see all those
building blocks– but the non-covalent
structure, how you could zipper apart
the two strands of DNA and make copies of both of
them and replicate DNA and then go forward.

That was an amazing
step forward, and for that, there was
a Nobel Prize awarded. Unfortunately it was
after Franklin's death. So it was given to Watson
and Crick and a third person. Now, here's has that
structure of DNA. I could sort of watch it
for hours to be honest. The phosphodiester background–
backbone going up the back, and the bases base
pairing across. And these are the key steps
that happened from the '50s. So in the definite–
after the definition of the double stranded
structure, it took a few years, but they cracked what's
known as the genetic code. How does that DNA get
converted into a protein? What happens is you make
an RNA copy of the DNA. And the RNA is read
to make a protein. And you will learn about
all those components. But that was another
real landmark. Then what was really exciting
is that some technology companies started
figuring out, first, there were very slow ways
to sequence DNA. But in the– and that
happened in 1977. But what was really important
is about a decade later, where the ability
to sequence DNA was not done anymore
using huge agarose gels and a bucket of radioactivity.

But it was done through
using fluorescence, in order to allow you to
read out the sequence of DNA. And you will learn about that. And in 1987, the
instruments were commercialized, major, major
technology and engineering. We wouldn't be
anywhere without that. In 1990, the Human
Genome Project began. In '01, the draft of the human
genome sequence was completed. 2010, you could
sequence a single strand of DNA, one molecule of DNA. And now there's so
many initiatives that have come out of that. And so much amazing
technology that has evolved. So things like the
1,000 Genomes Project to look at variation
across man, so all people from all different
parts of the world. You can look up that website. That's very cool. The Human Cell Atlas, there
was quite a bit of news about that in MIT
Technology News, where Aviv Regev is playing
a major part in that, to actually sequence
representatives from all of your trillions of
cells and see how they differ. And then there's cancer genome
projects and precision medicine sequence every type
of cancer cell, find out what's
different about it, and precisely figure
out how to treat it, all very exciting things.

And then of course, there's
synthetic genomes, where you can literally build
a cell and its genome, program it to do what
you want, hopefully. And then there's
one of the things that your generation
will have to deal with, and that's all the data. Because we've just found
ways to churn it out. But you guys are going to have
to do the heavy lifting there. So DNA, then, looking
at that structure, is packaged into cells. So figure this one out. Each human cell has 1.8
meters of DNA in it, yet it fits into a cell that's
10 to 100 microns in diameter. And it's bundled tightly up. So you'll learn how DNA in cells
gets bundled up and wrapped around proteins that
neutralize the negative charges of the double stranded DNA with
positively charged proteins and enable packaging. So we will talk
about all of this.

When is DNA unraveled? What signals its unraveling? Because in order to copy
it, you've got to unpack it. So these are a lot
of details about DNA that you'll be able to sort of
have much more sense of as we move forward. Cells are different in size. I just mentioned to you
a typical eukaryotic cell is about 10 to 100
microns in diameter. A typical bacterial cell
is about 1 to 10 microns. So there is a vast
difference in sizes for these simple cells
that have no nucleus, relative to the cells
that are compartmentalized and perform a lot of functions. So we will learn to appreciate
that difference in size, looking at the building blocks
that go into all of them, but then understanding
how big cells have to have a lot more
complexity in their signaling in order to establish
their functions but also interact with
other cells in multicellular organisms.

We're still doing
fine for time, yes. The other thing that we will
spend several classes on is imaging and visualization
of things going on in cells. So what we'll talk to you
about is the discovery of fluorescent proteins,
which have provided an unparalleled opportunity
to label proteins within living organisms in
order to track what they do. And through the efforts
of protein engineers, there is an entire panel
of colored proteins that fluoresce at
different wavelengths that we can use to study biology
in live systems, in real time.

These slides show you
a little bit of that. I love these pictures, just
showing a dividing cell. Where the chromosomes you
see red because the histones are labeled with red
fluorescent protein, and all that green fuzzy
stuff are microtubules around. We can do this now. You couldn't do this 15 years
ago, observe these changes. We can also look at changes
as cells divide and go through the cell cycle. One of my favorites
is this where of going through the stages
to program a cell to divide, a new protein gets made,
and then it settles down. But then when you go to divide
again, you keep making– you cyclically make
different sets of proteins. And you can observe them
in real time dividing. So just think if you were trying
to make a chemotherapeutic where you wanted to
stop cell division, or you wanted to inhibit
one of those proteins, you could literally
watch it function. Does it get in to cell? Does it disrupt the normal
pattern of cell division? So these are capabilities that
are now, really are available.

So I've talked to
you about cells. But I'm going to pass you
over to Professor Martin for a little bit– you'll get
a little bit of a sense of how he thinks. And then I'll do the wrap up. PROFESSOR MARTIN: Thank you. So this is one of my
favorite model organisms. This is a fruit fly, at
larger than real size. And so one topic that
I'll start on when I start lecturing either
at the end of this month or beginning of October is
we'll talk a lot about genetics. And one thing we'll start
on is pioneering research done in this system to
establish the chromosome theory of inheritance. OK. And we'll talk about the
importance in model organisms in discovering new biology. But in addition to
that, I also want to talk about how genetics will
affect you guys as you go on and graduate from MIT and
go into your own careers. Because genetics is really
playing an important role in all our lives. And already, you
guys have the option to get your DNA
genotyped, right.

There are lots of companies now
like 23andMe and Ancestry.com where you can get
your DNA genotyped. And you can learn
about your ancestry. You can learn about whether
you might be predisposed towards certain diseases. And so in order to appreciate
the data you get back from these companies, you really
have to understand something about genetics. And another thing which
I find very fascinating are ethical issues that come
up with the use of such sites. And you might have seen this
in the news last semester. Both forensic experts
and police identified a suspect in a killing
that happened 40 years ago.

And this was in part due to
using the suspect's family tree. OK. And so they used the family
tree, you know, some– you know, this guy's relatives
had done one of these Ancestry.com's. And they used the
information from DNA acquired from other
individuals to track down this other individual. OK. So one thing that I
find incredibly exciting about biology is that
it is truly dynamic. OK. And this is a human neutrophil. And it's just a bright
field microscopy. Nothing's labeled. And what you're
seeing here is this– this neutrophil is chasing
after this bacterium.

And it illustrates
another concept that we'll talk about in this
course, which is signaling. So this neutrophil
is receiving a signal from this bacteria that
tells it where it is. And it's then able to chase that
bacterium and track it down. And there you see it
just got the bacterium. OK. So we'll talk about dynamic
processes that cells do and how that's important
for their function.

In addition to
considering single cells, we also want to understand
how entire organisms and tissues work. And I want to
emphasize that, yes, we have sequence– or
researchers have sequenced the human genome and the genomes
of many different organisms, OK. And that's great, right. We have this data set. But we still don't understand
how all the components that are in the genome
are wired together and work in order to create
a complicated organism like ourselves. OK. And so one aspect of
that, which is mysterious, is how does the
genome encode shape? OK.

How do we get our
shape, and how do we get the shape of our organs? And this is something that
my lab is interested in. And so this is a
fruit fly embryo. And you can see at
the beginning here, this is three hours
into development. You just have a smooth
surface for this embryo. But during development,
this changes. And I'm just showing
you here a cross-section of the same embryo. And you see, it's
a sheet of cells that surrounds a central yolk. OK. And this changes three
hours into development, because a population of about
1,000 cells in this organism fold to form a crease. OK. So this is a dramatic shape
change for this embryo. It goes from being
a single layer to now having multiple layers. So this is a time
course here, showing you how cells change
shape in this tissue and how this leads
to what's initially a single layer of cells to
become two layers of cells.

And this process is similar
to morphogenetic events that happen in human embryos. But we can study this in fruit
fly embryos or many other model systems, in order to try to
understand mechanistically how this happens. So again, this is dynamic. And I want to show you
a movie that shows you the dynamics of this process. So now this is an embryo
that's been labeled with some of these
fluorescent proteins that Professor Imperiali
just introduced. One's green, that's the– and it's shown here in green. And the other is a red
fluorescent protein in red. The red fluorescent protein
is marking individual cells. The green protein is a motor
protein that generates force. And what you see is, where
the motor protein is, this is where the
tissue contracts.

And this is where
the tissue folds. OK. And so because we're able to
see these proteins in action, we can infer how they're
functioning during development to essentially
program tissue shape. And there are many
other opportunities where, even though
we have the genome, we still don't understand
how collectives of proteins, or collectives of cells,
are sort of interacting with each other to sort of
create emergent properties that are what are responsible
for patterning something as large as a human.

Another thing that we'll talk
about is how cells divide. And this is another
fruit fly embryo. And it's labeling histones. So it labels the DNA. And so you're seeing nuclei
here divide sequentially. There'll be one more division. And then it's going to stop. OK. And my point here is
that cell division during development and in adults
is under exquisite control. OK. And a breakdown
of this control is important in the
progression of cancer. So we're going to talk about
how cells control whether or not they divide, and how this
is impacted in cancer cells. I also want to point
out that this video is from Eric Wieschaus who is
at Princeton University. OK. Want to just hit the lights. I have one last thing
just to mention.

So I just want to reinforce
what Professor Imperiali said, we have a small class. So this is really an
opportunity to have this be more interactive
than it would be if we had like 300 people in the class. So I want to really encourage
you guys to ask questions. Also if you have ideas, we
would love to hear them. And I want to try one
new thing this semester. So I find that students
are a little hesitant to come to my office hours. So this year I want to hold
what I'm calling running hours. So one thing that I really
like to do is I like to run. And I've noticed that
many of my students are also runners, because
I'll like see them out around the river. And so I just want to hold
sort of weekly running hours. I'm going to choose 3 o'clock,
not three hour run, all right, 3:00 PM on Fridays. And we'll just
meet in my office. And so if you like to run,
you can just meet there. We'll go on a run
around the Charles.

And this is not a
competitive event. I'm not some fitness nut. I ran home last week, and I
ate half a bag of Swedish fish on the way. So it's not a competition. It's just to try to
get to know you guys and to try to break the ice
in sort of a non-academic way. BARBARA IMPERIALI: OK. So I'm just going
to wrap up here. So we bombed you with quite
a lot of– yes, over there. You want to know
more about running. [INAUDIBLE] AUDIENCE: Will you still
have normal office hours. PROFESSOR MARTIN: Yeah I'll
have normal office hours. Yeah, or you could
join me at CrossFit if you would like as well. We will both have office
hours, and we will post them.

And we welcome you to come
visit us and, you know, find out more, tell us
more about yourselves. We are fountains of information. So basically over the
first half of the course, we tend to cover foundations. And so we build on biochemistry,
one of my favorite subjects, where we cover all of
the molecules of life. What are all the bits it takes
to make a cell, lipids, sugars, proteins, nucleic acids.

Then we synthesize
them all together, where we show, in
molecular biology, how the genome
encodes the proteome, and what happens to the
proteome after that. So you'll see me for
all of those lectures. Then I will hand you over to
Professor Martin for genetics, for the learning how
to manipulate DNA. And we'll cap-off this
first phase of work with cell signaling
and understanding much more about
dynamics of cells, as opposed to static
building blocks. But you've got to understand
the building blocks before you can understand the complexity. That's why I really like
to cover those molecules at a reasonable depth. It's kind of
ridiculous, 4 classes. But nevertheless,
that's how we start. For some of you, you've
seen some of it before.

For others, you've
seen none of it before. It doesn't matter. We will give you
our flavor on it. If your chemistry
is a little weak, I suggest you read the textbook. There's a couple of sections
on just chemical covalent and non-covalent
bonding, that you'll need to do the first P set. If your chemistry is
strong, you're fine. If your chemistry is weak
and you need a little help, I'll run an extra
session next week. We can take care of
every eventuality because you're a smaller class. And then we'll
take it from there. And then what I
really want to do is encourage you
to do the reading. Make sure you're
in a recitation. And next time, but
it's in the sidebar, I'd like you to take a look
at the sliding scale which shows you the dimensions of
molecules, macromolecules, and organisms, which I find
rather cool, even though it's probably built for
high school students.

OK. That's it from us for now.

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