Download sweedler strategic plan - University of Illinois Archives

Beckman Institute
Strategic Plan
For Advanced Science and Technology
So, if you just add glia to the mix you can incorporate the work my and your labs are
trying to put together right now on neuronal-glial interactions. I’ve made a few strategic
changes to add that flavor. I also suggest where it might be valuable to include Bruce
Wheeler.
-bill
Initiative 23: Initiative on Neural Repair
The Goal
Can we repair nervous system damage, the catastrophic consequences of which have resisted
reversal by present drug and surgical interventions? The intransigence of brain damage and
disorder to treatment is of rising concern as many incurable conditions (Parkinson’s disease,
Alzheimer’s disease, schizophrenia, depression) have huge economic costs and will increase
with the aging of our population. This initiative seeks to discover novel insights, solutions and
applications for neural repair and restoration of function through targeting critical molecules and
processes that construct micro-networks during the normal wiring of the nervous system.
Centered at the interface between engineering, chemistry and neuroscience, this initiative boldly
proposes a multi-level model, from molecule to microcircuit, with a novel drug-discovery target.
Our focus is on developing advanced microanalytical approaches to understand the
spatiotemporal modulation of normal and damaged neurons in real time. The goal is to achieve
new insights into local micro-environments and information processing, signal integration,
molecular computation and cellular changes of state that result in long-term alterations in
neuron-neuron and neuron glia interaction within defined, controlled microcircuits or other
simplified preparations. By using technologies newly developed and applied at Beckman
Institute, we will undertake dynamic assessments, deciphering simultaneously multiple signals
and substrates of change in a model that closely simulates the complex natural
microenvironments of the brain. How do neurons find their targets during development? What
happens when and after processes are injured? Can neurons be encouraged to reestablish
connections based on the correct signals in the extracellular space? How is this influenced by
supporting tissue such as macroglia and microglia? This initiative addresses such questions
using relatively simple two- or three-neuron model systems in which the neuron can be
physically adjacent or fluidically connected by spatially distinct areas using unique microfluidic
devices and analytical measurement schemes adapted to work with picoliter volume samples.
The purpose of this initiative is to acquire new insights into local signals that establish and enrich
neuron-neuron and neuron-glia interactions that will enable us to identify and implement key
effectors of repair. To achieve this end, our goal is to re-create the environment in and around
interacting neurons in a micro-engineered structure so that we can regulate the surface and
solution chemistry with spatial, temporal and chemical control sufficient to mimic the neuron’s
environment within the brain, to perturb this with pharmacological or physical agents and
determine the effect on the neuron, and, then, to use these insights to rebuild damaged
microcircuits. The initiative combines three separate intellectual areas: 1) fabrication of
microdevices and single neuron culture, progressing from the largest to the smallest, 2)
identification of local signals that selectively alter neuronal regrowth and synaptogenesis, and 3)
probing the criticality of the signaling elements in restoring proper wiring and function.
Challenges and Opportunities
APRIL 13, 2006
PAGE 1
Beckman Institute
Strategic Plan
For Advanced Science and Technology
The Challenge: This type of multi-modal, multi-site analysis of single neurons in real time is not
presently done, anywhere. Individual measures of single properties of neurons cultured in populations are
usually assessed. The study we propose will increase simultaneous measurement parameters and reduce
the scale to subregions of individual neurons, and then to circuits formed by very few cells. Such work is
risky, but potentially transformative because of its detail of scale, breadth of parameters and length in the
time domain. It will provide one of the most complete insights into dynamic processes of change in the
single computational unit, the neuron, and its near-neighbor relationships. New and profound insights
into normal and abnormal neuronal function will result.
The Opportunities: There is a cadre of expertise in neuroscience, analytical measurements,
biomedical engineering and material science located within and near the Beckman Institute. This
initiative sits at the intersection of the three main research themes at the Beckman Institute, and
also is timely because of its interaction with the Bioengineering program and translational
research efforts. The unique opportunity presented here is to combine these strengths into a
unique enterprise to work on an important problem fundamental to neuroscience.
Specific Goals
To create an interdisciplinary program to study neuronal repair at the cellular level with a unique
set of engineering and measurement capabilities, using a range of neuronal model systems.
Specific goals include the development of neuronally compatible microdevices that can sample,
contain and manipulate the extracellular environment and distinct regions of a neuron under a
variety of different size ranges. Interface these devices to allow mass spectrometry, capillary
electrophoresis, optical microscopy, and electrophysiological measurements. Use several welldefined neurons from a range of biological models from invertebrates to vertebrates, to
investigate the extracellular space of a pair of neurons as they form synapses, sample and
measure the chemical cues involved, and validate the approach using several known trophins of
neural and glial origin. Finally, to investigate the chemical microenvironment during dynamic
responses to injury, and determine the molecular cues involved in axonal repair, synapse
formation and restoration of function.
Current status: This is a new initiative that builds on the work initiated and started with the
support from a grant from the Wm. Keck Foundation. In the first two years of support, several
interdisciplinary teams have been assembled, and the first publications on the engineering and
sampling aspects of the devices have appeared. This initiative uses the unique mass
spectrometric imaging and measurement capabilities available in the Sweedler group at the BI, as
well as the fabrication facilities available both at the BI and nearby facilities.
Development of new microdevices is critical to achieving maximal control of the
microenvironments surrounding different subregions of an individual neuron and, later, of
neuronal microcircuits. This experimental model will closely resemble the natural situation
where different neuronal regions have distinct chemical microenvironments. New ways of
assessing the microenvironment and subregions are critical because unlike the majority of cell
types, the neuron forms extensions into regions distant (millimeters) from the cell body and far
from each other. These elongated processes, the dendrites and axon, become conduits of
information processing and flow. Specialized points of synaptic communication can form at any
APRIL 13, 2006
PAGE 2
Beckman Institute
Strategic Plan
For Advanced Science and Technology
of these diverse neuronal sites. Long-term changes in synaptic interactions at one or several
extensions are the site(s) of change induced by experiences that underlie long-lasting functional
changes, including memory formation. Few specific synapses have been studied during these
dynamic changes in structure and function, as they decline with damage or disease, or as they are
remodeled to restore function. (Bring Wheeler’s expertise into this discussion.)
Five-year goal: With continued Institute, UIUC, and Foundation support, and using the
considerable strengths in bioengineering, materials chemistry and fundamental neuroscience, we
can become the preeminent group working towards understanding neuronal repair at the cellular
domain. Related five year goals include: (1) secure external support for a larger cadre of
scientists and engineers working on these efforts; (2) Offer opportunities for graduate and
undergraduate students, as well as postdoctoral fellows, to engage in research with distinguished
faculty neuronal repair.
Resources: Currently the center is supported by funds from Wm. Keck Foundation with a
campus match. Most importantly, we request that UIUC make the Initiative on Neural Repair
targeted development effort in its upcoming campaign. We also anticipate continued additional
resources from external research funding sources and corporate contracts.
Who’s responsible: Neurotech group. Professors Jonathan V. Sweedler, Martha Gillette and
Ralph Nuzzo form the core of the Keck effort. However, this initiative seaks to expand these
effort to members of several BI themes, including…
APRIL 13, 2006
PAGE 3
Beckman Institute
Strategic Plan
For Advanced Science and Technology
APRIL 13, 2006
PAGE 4