Nov 21 2016 02:00 PM
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Nov 21 2016 03:00 PM
Abstract:
Protein
interactions are a key building block of biological networks
controlling the flow of information, energy and metabolites. The
engineering of multi-protein systems is therefore an important, but
currently
underexplored, area of synthetic biology. I outline a protein systems
engineering framework that uses protein-protein interactions as its
basic building block. The systematic combination of protein docking and
molecular dynamics simulations revealed considerable
complexity already in the simple binding of two proteins. Nevertheless,
this complexity was tamed experimentally through the recombination of
flexibly connected interaction modules. Following this strategy,
carefully chosen or computationally designed helper
modules amplified and "normalized" the real-time detection of protein
binding events (hiFRET). This now opens the door to the construction of
genuine protein computation circuits with various applications from
cheap CRISPR-based DNA biosensors to smart biologicals
for cell therapy.
Currently,
such bioengineering is held back a large gap between our very limited
capacity to experimentally characterize biological building blocks or
actual designs, on the one hand, and a wealth of candidate
parts and hypothetical designs suggested by bioinformatic analysis or
modelling, on the other hand. I propose a novel research platform that
bridges this gap by integrating robotic DNA assembly with cell-free
expression, microfluidics and advanced interaction
sensors. This platform will not only enable rapid protein circuit
engineering but will also be geared towards metagenome-scale
characterization of enzymatic activities as well as the combinatorial
assembly of biosynthesis pathways for drug screening or metabolic
prototyping.
Biography:
Raik Grünberg is a synthetic biologist with roots in
computational biophysics and experimental protein design. After studying
Biochemistry at the University of Leipzig (Germany), Raik performed his
PhD in biophysics at the EMBL in Heidelberg (Germany)
and the Pasteur Institute in Paris on the automated modelling and
atomic-detail simulation of protein complexes. This resulted in a widely
quoted mechanistic model of protein-protein binding and pushed the
boundary of what was considered technically feasible
in protein-protein docking. As a postdoc at the Center for Genomic
Regulation (CRG) in Barcelona, he entered the emerging field of
synthetic biology and set the ground work for the experimental design of
synthetic protein systems. He then took up a research
associate position at the University of Montreal (Canada) where he
started up a new protein synthetic biology lab and sub-group. He is
currently offering consulting services on the robotic automation of
molecular and synthetic biology workflows and is a visiting
researcher at KAUST.
Raik
has received a Boehringer Ingelheim Foundation PhD fellowship and Marie
Curie as well as Human Frontier Science Program (HFSP) postdoctoral
fellowship awards. Raik is co-founder and editor of the Synthetic
Biology Open Language (SBOL), an international effort connecting key
industry and academic players to set standards for an emerging tool
stack of automated biological design. Typical for his role at the
interface of computational and experimental bioengineering,
he is also serving as the chair of the iGEM software track.
Website: http://raiks.de/research.html