Laboratory of Biological Networks
Department of Biomedical Engineering
Institute for Genome Sciences & Policy
University Program in Genetics & Genomics
Center
for Biomolecular & Tissue Engineering
PI: Lingchong You
(CV)
Assistant Professor
Contact:
CIEMAS 2345
Phone: 919 660 8408 (Office), 919 684 3566 (Lab)
FAX: 919 668 0795
Email:
you (at) duke.edu
Open positions
We invite motivated
individuals to join us in exciting research in synthetic and systems biology. Active
projects include engineering of synthetic ecosystems, bacterial killer circuits
and microbial swarmbots for therapeutic applications, analysis and
reprogramming of mammalian cell cycle, and information processing by gene
circuits.
o Lab
technician: A B.S. in biology or
related fields, familiar with microbiology and molecular biology techniques,
including but not limited to preparation of chemical and biological reagents,
cloning, bacterial culturing, and use of typical lab equipment.
o Postdoc:
A Ph.D. in Microbiology,
Genetics, Molecular Biology, Biochemical Engineering, or closely related
fields.
If interested, send your
CV to Lingchong You by email. Also arrange at least two recommendation letters.
For a postdoc position, one letter should be from your current primary advisor.
Research
Research
in my lab is at the interface of computation, engineering, and medicine. We
apply engineering tools and principles, such as control theory, information
theory, and reaction kinetics, to guide reprogramming of cellular behavior
using synthetic gene circuits. In the long term, these synthetic gene circuits
will find diverse applications, including novel systems for protein
engineering, metabolic engineering, drug development, gene therapy, and stem
cell reprogramming.
However,
programming of predictable cellular behavior is challenging. Unlike typical
engineered systems, cellular processes are intrinsically noisy. In each cell,
gene expression is subject to stochastic fluctuations due to small numbers of
interacting molecules, heterogeneity of intracellular environments, and
extra-cellular perturbations. Presence of cellular noise raises two fundamental
questions. First, how is nature able to assemble noisy, imperfect components
into robust systems that accurately carry out their functions? Second, as
bioengineers, how can we design synthetic gene circuits that will function
reliably despite cellular noise?
My lab approaches these questions from two
complementary perspectives. First, we combine mathematical modeling and
experiments to analyze dynamics of natural signaling processes, including cell
cycle regulation and cell-cell communication. Second, based on insights learnt
from these natural systems, we design and construct synthetic gene circuits
with well-defined functions. Implementation of these gene circuits will also
enable us to probe biological design strategies in a well-defined framework,
and to generate systems with applications in medicine and biotechnology.
Specifically, we are pursuing three highly synergistic directions:
Programming bacterial population dynamics: These projects aim to engineer synthetic gene
circuits that can precisely program bacterial growth, death, and aggregation in
complex environments, with implications for therapeutic and biotechnology
applications.
Cellular information processing: These projects aim to define characteristics of
information processing in the presence of cellular noise. A long term goal is
to engineer gene circuits to perform cell-based computation.
Analysis and reprogramming of mammalian cell
cycle: These projects aim to
analyze and perturb mammalian cell cycle regulation by modeling. Their will
provide insight into development of strategies to reprogram and interfere with
cell cycle regulation for cancer therapy.
News and profiles about our research
Synthetic
predator-prey system (2008)
Bistable
Rb-E2F switch (2008)
Student honored by
Goldwater foundation (2008)
Packard
award on studying cellular information processing (2006)
High school advisees
won national prize (2006)
Synthetic killer
circuits (2005)
Keck
Futures Initiatives Grant on engineering microbial swarmbots (2005)
Custom-Made
Microbes, at Your Service (NY Times article) (2004)
Teaching
o BME265 (Spring 2005, Fall 2006). Modeling Gene Expression and
Cell Signaling
o BME100 (Spring 2006, Spring 2007, Spring 2008).
Modeling cellular and molecular systems
Lab
members
Postdoctoral associates (previous
institution)
o Hao Song (University
of Texas at Houston Medical
Center
o Jeff Wong (University
of Toronto
Graduate students (undergraduate
institution)
o
Tae Jun Lee (Duke
University
o
Philippe Marguet (Cornel
University
o
Anand Pai (University of Mumbai , India
o
Chee Meng Tan (National University of Singapore
o
Yu Tanouchi (Keio
University , Japan
Undergraduate
students
o
Stephanie Chang
o
Stephen DeVince
o
Yingte Huang
o
Meagan Gray (Pratt fellow)
o
Cameron Smith (Pratt fellow)
o
David Wang
Publications
2008
o F.
Balagadde, H. Song, J. Ozaki, C. Collins, M. Barnet, F. H. Arnold, S. Quake,
and L. You (2008). A synthetic Escherichia coli predator-prey ecosystem. Molecular Systems Biology. Published
online. April.
o G. Yao, T. Lee, S. Mori, J. Nevins#, and L. You# (2008). A
bistable Rb-E2F switch underlies the restriction point. Nature
Cell Biology. Published online (# corresponding authors)
o T. Lee, G. Yao, J. Nevins, and L. You (2008). Sensing and integration of Erk and PI3K
signals by Myc. PLoS Computational Biology. 4(2):
e1000013. doi:10.1371/journal.pcbi.1000013
o J. V. Wong, H. Song, and L. You (2008). A
whole more than the sum of its synthetic parts (Point of View). ACS
Chemical Biology. 3(1):27-9.
2007
o
C. Tan, F.
Reza, and L. You. Noise-limited
frequency signal transmission in gene circuits. Biophysical J. Published
online (2007)
o
C. Tan, H.
Song, J. Niemi, and L. You. A
synthetic biology challenge: making cells compute. Molecular BioSystems. 3:343 (2007).
o
P. Marguet,
F. Balagadde, C. Tan, and L. You. Biology by
design: reduction and synthesis of cellular components and behavior. J.
Royal Society Interface. 4:607(2007)
o
D. Tu, J. Lee, T.
Ozdere, T. Lee, and L. You. Engineering gene circuits:
foundations and applications. In Nanotechnology in Biology and Medicine
Methods, Devices and Applications, Ed. T. Vo-Dinh. CRC Press. Chapter
21. (2007)
o
T. Lee, C. M.
Tan, D. Tu, and L. You. Modeling cellular
networks. In Bioinformatics: An Engineering Case-Based Approach, Eds. G. Alterovitz & M. Ramoni. Chapter
6. (2007).
2006
o
H. Song and L. You. Evolving
Sensitivity (Point of View). ACS Chemical Biology. 1:681(2006).
o
L. You and J. Yin. (2006). Evolutionary
design on a budget: robustness and optimality of bacteriophage T7. IEE. Systems Biology. 153:46-52.
2005
o
F. K. Balagadde *, L. You*, C. Hansen, F. H. Arnold and S. Quake.
(2005). Long-term
monitoring of bacteria undergoing programmed population control in a
microchemostat, Science. 309: 137-140 (* contributed equally).
2004 and before
o
L. You, R. S. Cox III, R. Weiss,
and F. H. Arnold. (2004). Programmed
population control by cell-cell communication and regulated killing. Nature. 428: 868-871.
Featured in ScienceNow
(405:3).
o
L. You, (2004) Towards computational
systems biology. Cell
Biochemistry and Biophysics. 40: 167-184
o
L. You, A. Hoonlor, and J. Yin. (2003) Modeling biological
systems using Dynetica – a simulator of dynamic networks. Bioinformatics. 19: 435-436. Click here
to see more
o
L. You and J. Yin (2002). Dependence
of epistasis on environment and mutation severity as revealed by in silico mutagenesis
of phage T7. Genetics. 160: 1273-1281
o L. You, P. F. Suthers, and J. Yin (2002). Effects of E. coli physiology on growth of phage
T7 in vivo and in silico. J. Bacteriology. 184: 1888-1894. (Highlighted in Editors
Choice of Science (2002), 296:
219)
o L. You and J. Yin (2001).
Simulating the growth of viruses. Proceedings of the Pacific Symposium on
Biocomputing: 532-543.
o L. You and J. Yin
(2000). Patterns of regulation from mRNA and protein time-series Metabolic Engineering. 2: 210-217.
o D. Endy, L. You,
J. Yin, and
o L. You and J. Yin (1999). Amplification and spread of
viruses in a growing plaque. J. Theor. Biol. 200(4): 365-373.
o L. You, Q. Liu, Y. Shi, C. X. Wang, M. Lahaye, and V. Tran
(1997). The conformational study of b-D-GlcA-(1,4)-L-Rha in solution by NMR and molecular dynamics
simulations. Chemical Physics. 224:
81-94.