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Hi I'm Cynthia Walberger and
I'm a professor of biophysics and biophysical chemistry
at the Johns Hopkins School of Medicine.
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My team and I study molecular signals and
how they regulate events in the cell.
One of the things we're trying to understand is how
the attachment of the small protein ubiquitin regulates many
different types of events in the cell.
So let's see what we can find in the toy box to help explain our
research.
[SOUND] Oh here, this is great.
So, ubiquitin is a small protein, and
it can be attached to other proteins, and
serves as sort of a signal for something to happen.
Now, one of the cool things about ubiquitin is that you can
attach one ubiquitin to another protein or
you can make a chain of ubiquitins.
So here's one kind of chain of ubiquitins,
but you could assemble them in different ways to form different
types of chains.
So now I'm going to assemble them using this sort of
hole on the side.
So now again I have three ubiquitins in a chain but
that looks different from the first chain I showed you.
And it turns out there are many many different ways in which
these can put together.
And each of these types of chains
represents a different signal.
We're focused on understanding in this very fundamental way, so
how do these different types of chains get assembled,
how are they recognized as distinct signals and
then how do they get very specifically disassembled?
At the right time when we're done and we don't need that
signal attached to this protein anymore.
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So how does a cell turn a gene on or turn a gene off?
Well it turns out it's a pretty complicated process.
But one of the ways, in which it does, is by attaching chemical
tags to the proteins that actually package our DNA.
So I'm gonna use this string here,
to represent a piece of our genomic DNA.
And, so this may be how we represent DNA, but
actually the DNA in our cells is packaged up by being wrapped
around these protein cores kind of like the way I'm doing
here with these wooden sticks.
One way in which the cell has for signaling that we need
to do something, let's say turn the gene on in this region,
is it can attach a variety of chemical tags.
So, some of these chemical tags are just these very small
little chemical groups that are just made up of a few atoms.
So, they're sort of,
I'm representing them as these small pieces of clay, but
another kind of signal that gets attached is ubiquidon.
So there might be a single ubiquitin protein that's
attached in a particular location to these disks of
proteins, actually are called histones.
We're studying the enzyme complex that removes this
modification in yeast and we use that as a model system for
understanding how the process works in human cells.
Now, in human cancer types that are particularly resistant
to chemotherapeutic agents that we have available to us today,
it turns out that the human equivalent of this enzyme that
removes this very ubiquitin modification from histone
proteins is made at very high levels and is over active at
removing ubiquitin from these histone proteins.
So our hope is by understanding how this process works at a very
molecular level, we can come up with new ideas and
new avenues for identifying or designing chemotherapeutic
agents that might treat these cancers for which,
at present, there really are no effective treatments.
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