Seminar – MPFI Seminar Series

Tools for Analyzing and Repairing the Brain

May 26,
  • Time:
  • Location: MPFI - Elmore Auditorium
  • Host: Yingxue Wang

Understanding and repairing
complex biological systems, such as the brain, requires technologies for
systematically observing and controlling these systems. We are
discovering new molecular principles that enable such technologies. For
example, we discovered that one can physically magnify biological specimens by
synthesizing dense networks of swellable polymer
throughout them, and then chemically processing the specimens to isotropically swell
them. This method, which we call expansion microscopy, enables ordinary
microscopes to do nanoimaging – important
for mapping the brain across scales. Expansion of biomolecules away from
each other also decrowds them,
enabling previously invisible nanostructures to be labeled and seen. As a
second example, we discovered that microbial opsins, genetically expressed in
neurons, could enable their electrical activities to be precisely controlled in
response to light. These molecules, now called optogenetic tools, enable
causal assessment of how neurons contribute to behaviors and pathological
states, and are yielding insights into new treatment strategies for brain
diseases. Finally, we are developing, using new strategies such as
robotic directed evolution, fluorescent reporters that enable the precision
measurement of signals such as voltage and calcium. By fusing such
reporters to self-assembling peptides, they can be stably clustered within
cells at random points, distant enough to be resolved by a microscope, but
close enough to spatially sample the relevant biology. Such clusters, which we
call signaling reporter islands (SiRIs), permit many
fluorescent reporters to be used within a single cell, to simultaneously reveal
relationships between different signals. We share all these tools freely,
and aim to integrate the use of these tools so as to enable comprehensive understandings
of neural circuits.