Genome Architectures Spatial Transcriptomics - The Siyuan Wang Lab

Transcript

• 00:06Each of our cells
• 00:08have about six feet of
• 00:10genomic DNA,
• 00:11and it's packaged in a
• 00:12cell nucleus that's about ten
• 00:14micron in diameter.
• 00:16The ratio of this packaging
• 00:17is about the same as
• 00:19packaging the whole circumference of
• 00:21Manhattan into a soccer ball.
• 00:23So the three d genome
• 00:25organization
• 00:26on the biological front is
• 00:27actually linked to many essential
• 00:29genomic functions. And also when
• 00:31it goes awry, it's linked
• 00:32to all kinds of diseases
• 00:33and also aging.
• 00:38We are quite a technology
• 00:40driven lab. We develop state
• 00:42of the art image based
• 00:44spatial omics technologies.
• 00:46We're quite well known for
• 00:48developing such technologies for studying
• 00:50the three d genome organization.
• 00:52Although in recent years, we're
• 00:53also branching out to other
• 00:55modes of spatial omics, such
• 00:57as spatial transcriptomics and and
• 00:59spatial epigenomics.
• 01:00We also apply these technologies
• 01:02that we develop into different
• 01:04areas of biological study as
• 01:06well, particularly with a focus
• 01:08on cancer, aging, and immuno
• 01:09biology.
• 01:14The whole lab actually started,
• 01:16based on a technology I
• 01:18developed in my post shock
• 01:19phase called the chromatin tracing.
• 01:21So it was the first
• 01:22in kind image based genomics
• 01:25technology that really really opened
• 01:26up this subfield of three
• 01:28d genome organization.
• 01:30And this allows
• 01:31us to essentially trace the
• 01:33three d folding organization of
• 01:35the DNA or the genome
• 01:37directly by imaging.
• 01:38But the one issue we
• 01:40had is if you want
• 01:42to discover new regulators of
• 01:44the three d genome, it's
• 01:45very low throughput.
• 01:47We basically developed another technology
• 01:49called perturb tracing
• 01:50to address that. We combined
• 01:53pooled whisper screen
• 01:55technology
• 01:56with
• 01:56the quantum tracing technology.
• 01:58And we developed a new
• 02:01in situ barcoding
• 02:02and the decoding technique
• 02:04that allows us to
• 02:06distinguish which cell has which
• 02:08perturbation
• 02:09and at the same time,
• 02:10in the same cells,
• 02:12trace their three d folding
• 02:13organization.
• 02:14So this allows us to
• 02:16screen for hundreds of potential,
• 02:18regulators of the three d
• 02:19genome organization.
• 02:25If we can find a
• 02:26way, for example, to use
• 02:27this three d genome regulators
• 02:29as handles
• 02:30to either halt
• 02:32or revert the deleterious
• 02:34three d genome changes during
• 02:36diseases such as cancer,
• 02:38Or if,
• 02:40for example,
• 02:41some protein is a downstream
• 02:44effector of the three d
• 02:45genome.
• 02:46Maybe just by removing that
• 02:47protein,
• 02:49one can have beneficial effect
• 02:51to the patient.
• 02:53So either from the upstream,
• 02:55correct the three d genome,
• 02:56or from the downstream, block
• 02:57the factor that leads to
• 02:59diseases.