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
Selected awards and activities
o
DuPont Young
Professor Award. 2008
o
David and Lucile Packard
Fellowship. 2006
o
Invited speaker.
Synthetic Biology Discussion Meeting (Sponsored by the Royal Society). June
2008.
o
o
Invited speaker.
Life Engineering Symposium (Sponsored by the National Academies). August 2005,
SF, CA.
o
Marie Christine Kohler Knapp Fellow. University of Wisconsin-Madison. 2001–2002.
o
Editorial Board:
Synthetic
Biology
Systems and Synthetic Biology
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 (
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 (2005-). Modeling Gene Expression and
Cell Signaling
o BME100 (2006-). 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
Mark Hallen (Duke University
o
Tae Jun Lee (Duke University)
o
Philippe Marguet (Cornel
University
o
Anand Pai (U of Mumbai , India
o
Stephen Payne (MIT; DHS Fellowship)
o
Chee Meng Tan (National University of Singapore
o
Yu Tanouchi (Keio
University , Japan
Publications
(feel free to contact me for PDF preprints
or reprints)
2009
o H.
Song, S. Payne, M. Gray, and L. You
(2009). Spatiotemporal modulation of biodiversity in a synthetic,
chemical-mediated ecosystem (Under review).
o C.
Tan, P. Marguet, and L. You (2009). Emergent
bistability by a growth-modulating positive feedback circuit (Under review).
o A.
Pai, Y. Tanouchi, C. Collins, and L. You
(2009). Engineering multicellular behavior by cell-cell communication (Under
review)
o A.
Pai and L. You (2009). Optimal
tuning of bacterial sensing potential. Molecular Systems Biology. In press.
o
Y. Tanouchi, A. Pai, and L. You (2009). Decoding
biological design principles using gene circuits (2009). Molecular
BioSystems (Synthetic Biology Theme Issue). DOI: 10.1039/b901584c
o F. J. Isaacs,
and L. You (2009). A brave new synthetic world (meeting
report). Genome Biology. 10:302
o Q. Wang, J. Niemi, C. Tan, L. You, and M. West (2009). Image
segmentation and dynamic lineage analysis in single-cell fluorescence
microscopy. Synthetic Biology. In press.
2008
o
C. Smith, H. Song, and L.
You (2008). Signal discrimination by
differential regulation of protein stability in quorum sensing. J.
Molecular Biology. Published online
o
Y. Tanouchi, D. Tu, J. Kim, and L. You (2008).
Noise reduction by diffusional dissipation in a
minimal quorum sensing motif. PLoS
Computational Biology. 4(8): e1000167.
doi:10.1371/journal.pcbi.1000167
o
K. Brenner, L. You, and F. H. Arnold (2008). Engineering
microbial consortia: a new frontier for synthetic biology. Trends
in Biotechnology. 26: 483-489
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. 4:187. Faculty of 1000 Biology,
Must Read.
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. Faculty of 1000 Biology, Must Read.
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).
Faculty of 1000 Biology, Recommended.
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 R.
Srivastava, L. You, J. Summers, and J. Yin (2002). Stochastic versus
deterministic modeling of intracellular viral kinetics. J.
Theor. Biol. 218: 309-321.
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.