Skin Diseases, Structural Biology & Crystallography - The Bunick Lab at Yale School of Medicine

Transcript

• 00:05The skin is the largest
• 00:07organ in the body. And
• 00:09not only is it a
• 00:10barrier, but it has a
• 00:11very active immune system. When
• 00:13we think of inflammatory
• 00:14skin disorders, psoriasis, when we
• 00:16think of atopic dermatitis, they
• 00:18all have a component of
• 00:19skin barrier disruption.
• 00:21And so many of the
• 00:22diseases in dermatology become a
• 00:24vicious cycle between skin barrier
• 00:26disruption and inflammation.
• 00:28Patients also experience things like
• 00:30itch,
• 00:31burning, stinging, and it affects
• 00:33their quality of life. And
• 00:35my job as the scientist
• 00:37is understanding how to break
• 00:38this loop.
• 00:46In the big picture, my
• 00:47laboratory is doing what is
• 00:48called structural biology. We are
• 00:50trying to understand the structure
• 00:52of how proteins,
• 00:54nucleic acids, and other macromolecules
• 00:56work in the skin and
• 00:58how drugs that target different
• 01:00skin diseases work. And then
• 01:02in certain genetic diseases where
• 01:04those proteins
• 01:05are in error, we want
• 01:07to understand what has gone
• 01:08wrong and how can we
• 01:09fix
• 01:11it. There's no one else
• 01:12in dermatology
• 01:13that is running a primary
• 01:14NIH funded research lab that's
• 01:17dedicated to structural biology and
• 01:19answering those difficult
• 01:20biochemistry
• 01:21questions through the approaches of
• 01:23extra crystallography,
• 01:25cryo electron microscopy, and if
• 01:27needed, nuclear magnetic resonance imaging.
• 01:33So extra crystallography
• 01:35is a particular technique that
• 01:37allows you to understand the
• 01:38atomic level structure
• 01:40of proteins, nucleic acids, and
• 01:42their complexes.
• 01:44What you have to do
• 01:44in crystallography is take a
• 01:46very pure protein, for example,
• 01:48and put it in the
• 01:49right solution
• 01:50that allows it to precipitate.
• 01:52And when it does it
• 01:53just right, it forms a
• 01:54crystal. And that crystal is
• 01:56a perfectly
• 01:58aligned lattice of lots and
• 02:00lots of molecules of that
• 02:01protein of interest. And then
• 02:03when you hit that crystal
• 02:04with x rays, that crystal
• 02:06then diffracts
• 02:07the light. And then what
• 02:09we can do is use
• 02:10mathematical
• 02:10approaches to take that diffraction
• 02:12pattern and turn it into
• 02:14actually a three-dimensional
• 02:15model
• 02:16of that protein, and that
• 02:17allows us to determine the
• 02:19structure at that atom and
• 02:20bond level. And then we
• 02:21can take that information and
• 02:23ask those critical questions. What
• 02:25does this tell us about
• 02:26helping the human patient?
• 02:33One of the wonderful things
• 02:34about being a physician scientist
• 02:36is I get to see
• 02:37what it's like in the
• 02:38lab to make a discovery,
• 02:40but I also get to
• 02:41talk to patients face to
• 02:42face. And I really get
• 02:43an understanding of what matters
• 02:45to them.
• 02:46And the advantage of this
• 02:47is it allows me to
• 02:48then come back from a
• 02:50translational perspective and understand
• 02:52what is going to help
• 02:54deliver better patient care. This
• 02:57is also why I really
• 02:58am excited to be a
• 02:59part of clinical trials here
• 03:00in dermatology
• 03:01at Yale.
• 03:03I love helping patients. I
• 03:05love it when patients feel
• 03:07better and are happier with
• 03:08themselves.
• 03:09In the end, all of
• 03:10what we do, whether it's
• 03:11the research mission,
• 03:13the clinical mission, or even
• 03:14a clinical trial mission, it's
• 03:16all about advancing patient care,
• 03:18developing new therapies for rare
• 03:20genetic skin diseases for which
• 03:22patients have nothing yet.