articles | essays | chapters | preprints | posters
2024
R Martinez-Corral, K-M Nam, A DePace, J Gunawardena
"The Hill function is the universal Hopfield barrier for sharpness of input-output responses"
bioRxiv doi:10.1101/2024.03.27.587054 2024
2023
U Çetiner, J Gunawardena
"Universal bounds on information-processing capabilities of Markov processes"
arRxiv doi:2310.10584 2023
K-M Nam, J Gunawardena
"The linear framework II: using graph theory to analyse the transient regime of Markov processes"
Front Cell Dev Biol, 11:1233808 2023. Full text PDF.
Invited contribution to the Research Topic on Network-based Mathematical Modeling in Cell and Developmental Biology.
M Faizi, R T Fellers, D Lu, B S Drown, A Jambekhar, G Lahav, N Kelleher, J Gunawardena
"MSModDetector: a tool for detecting mass shifts and post-translational modifications in individual ion mass spectrometry data"
bioRxiv doi:10.1101/2023.06.06.543961 2023
J A Owen*, P Talla*, J Biddle, J Gunawardena
"Thermodynamic bounds on ultrasensitivity in covalent switching"
Biophys J, 122:1-13 2023. Full text PDF.
R Martinez-Corral, M Park, K Biette, D Friedrich, C Scholes, A S Khalil, J Gunawardena, A H DePace
"Transcriptional kinetic synergy: a complex landscape revealed by integrating modelling and synthetic biology"
Cell Syst, 14:324-39 2023. Full text PDF.
2022
U Çetiner, J Gunawardena
"Reformulating non-equilibrium steady states and generalized Hopfield discrimination"
Phys Rev E, 106:064128 2022. PDF.
K-M Nam*, R Martinez-Corral*, J Gunawardena
"The linear framework: using graph theory to reveal the algebra and thermodynamics of biomolecular systems"
Interface Focus, 12:20220013 2022. Full text PDF. Invited contribution to the Theme Issue on Time Keeping and Decision Making in Living Cells.
J Gunawardena
"Learning outside the brain: integrating cognitive science and systems biology"
Proc. IEEE, 110:590-612 2022. Full text PDF. Invited contribution to the Special Issue on Systems and Synthetic Biology.
press attention — Phys.Org (Ingrid Fadelli).
2021
J W Biddle, R Martinez-Corral, F Wong, J Gunawardena
"Allosteric conformational ensembles have unlimited capacity for integrating information"
eLife, 10:e65498 2021. Full text PDF earlier version on bioRxiv
S J Gershman, P E M Balbi, C R Gallistel, J Gunawardena
"Reconsidering the evidence for learning in single cells"
eLife 10:e61907 2021. Full text PDF.
press attention — The Scientist (Catherine Offord) Unexplainable podcast.
2020
F Wong, J Gunawardena
"Gene regulation in and out of equilibrium"
Annu Rev Biophys 49:199-226 2020. e-print
K-M Nam, B M Gyori, S V Amethyst, D J Bates, J Gunawardena
"Robustness and parameter geography in post-translational modification systems"
PLoS Comput Biol, 16:e1007573 2020. doi:10.1371/journal.pcbi.1007573 PDF
J W Biddle, J Gunawardena
"Reversal symmetries for cyclic paths away from thermodynamic equilibrium"
Phys Rev E, 101:062125 2020. PDF+SI
2019
J P Dexter*, S Prabakaran*, J Gunawardena
"A complex hierarchy of avoidance behaviours in a single-cell eukaryote"
Curr Biol 29:4323-9 2019. full text PDF+SI minor correction Wallace Marshall's commentary 
H1Connect
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HMS news The Scientist (Ruth Williams) ScienceNews ScienceAlert SciTechDaily ZME Science Live Science National Geographic (Russian) Batrachospermum Magazine (Russian) Numerama (French) Technologie Média (French) WDR5 Quarks (German radio broadcast 10 Dec 2019, segment 6-12mins) Swarajya (Indian, in English) Parsing Science Scientific American
A Barabanschikov, J Gunawardena,
"Monostationarity and multistationarity in tree networks of Goldbeter-Koshland loops"
Bull Math Biol 81:2463-509 2019. PDF
J Park, J Estrada, G Johnson, C Ricci-Tam, M Bragdon, Y Shulgina, A Cha, J Gunawardena, A H DePace
"Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity"
eLife 8:e41266 2019. Full text PDF
J W Biddle, M Nguyen, J Gunawardena
"Negative reciprocity, not ordered assembly, underlies the interaction of Sox2 and Oct4 on DNA"
eLife 8:e41017 2019. Full text PDF.
2018
D Agarwal, R T Fellers, B P Early, D Lu, C J DeHart, P D Compton, P M Thomas, G Lahav, N L Kelleher, J Gunawardena
"Analysing protein post-translational modform regions by linear programming",
bioRxiv doi:10.1101/456640, 2018.
C J DeHart, L Fornelli, L C Anderson, R T Fellers, D Lu, C L Hendrickson, G Lahav, J Gunawardena, N L Kelleher
"A multi-modal proteomics strategy for characterizing posttranslational modifications of tumor suppressor p53 reveals many sites but few modified forms",
bioRxiv doi:10.1101/455527, 2018.
J P Dexter, P S Ward, T Dasgupta, A M Hosios, J Gunawardena, M G Vander Heiden
"Lack of evidence for substrate channeling or flux between wild-type and mutant isocitrate dehydrogenase to produce 2-hydroxyglutarate"
J Biol Chem, 293:20051-61 2018. PDF Supplementary Figure
this paper was selected for a special virtual issue on cancer biology
F Wong, A Dutta, D Chowdhury, J Gunawardena
"Structural conditions on complex networks for the Michaelis-Menten input-output response"
PNAS, 115:9738-43 2018. doi:10.1073/pnas.1808053115 PDF SI
J P Dexter, J W Biddle, J Gunawardena
"Model discrimination for Ca2+-dependent regulation of myosin light chain kinase in smooth muscle contraction"
FEBS Letters, 592:2811-21 2018. doi:10.1002/1873-3468.13207 PDF
F Wong, A Amir, J Gunawardena
"Energy-speed-accuracy relation in complex networks for biological discrimination"
Phys Rev E, 98:012420 2018. PDF Supplementary Information arXiv:1710.06038[q-bio.MN]
P D Compton, N L Kelleher, J Gunawardena
"Estimating the distribution of protein post-translational modification states by mass-spectrometry"
J Prot Res, 17:2727-34 2018. doi:10.1021/acs.jproteome.8b00150 PDF Supplementary Information
R Aebersold, J N Agar, I J Amster, M S Baker, C R Bertozzi, E S Boja, C E Costello, B F Cravatt, C Fenselau, B A Garcia, Y Ge, J Gunawardena, R C Hendrickson, P J Hergenrother, C G Huber, A R Ivanov, O N Jensen, M C Jewett, N L Kelleher, L L Kiessling, N J Krogan, M R Larsen, J A Loo, R R Ogorzalek Loo, E Lundberg, M J MacCoss, P Mallick, V K Mootha, M Mrksich, T W Muir, S M Patrie, J J Pesavento, S J Pitteri, H Rodriguez, A Saghatelian, W Sandoval, H Schlüter, S Sechi, S A Slavoff, L M Smith, M P Snyder, P M Thomas, M Uhlén, J E Van Eyk, M Vidal, D R Walt, F M White, E R Williams, T Wohlschlager, V H Wysocki, N A Yates, N L Young, B Zhang
"How many human proteoforms are there?"
Nat Chem Biol 14:206-214 2018. PDF
2017
T Ahsendorf, F-J Müller, V Topkar, J Gunawardena, R Eils
"Transcription factors, coregulators, and epigenetic marks are linearly correlated and highly redundant"
PLoS ONE 12:e0186324 2017. Full text PDF.
M M Slabodnick, J G Ruby, S B Reiff, E C Swart, S Gosai, S Prabakaran, E Witkowska, G E Larue, S Fisher, R M Freeman Jr, J Gunawardena, W Chu, N A Stover, B D Gregory, M Nowacki, J Derisi, S W Roy, W F Marshall, P Sood
"The macronuclear genome of Stentor coeruleus reveals tiny introns in a giant cell"
Curr Biol 27:569-75 2017. PDF.
H Qi, C Despres, S Prabakaran, F X Cantrelle, B Chambraud, J Gunawardena, G Lippens, C Smet-Nocca, I Landrieu
"The study of posttranslational modifications of Tau protein by nuclear magnetic resonance spectroscopy: phosphorylation of Tau protein by ERK2 recombinant kinase and rat brain extract, and acetylation by recombinant CREB-binding protein"
Methods Mol Biol 1253:179-213 2017. PDF.
2016
J Estrada, F Wong, A DePace, J Gunawardena
"Information integration and energy expenditure in gene regulation"
Cell 166:234-44 2016. Full text PDF Supplemental Information.
For his contribution to this paper, Javier Estrada was awarded the Young Investigator Award at the 2016 International Conference on Systems Biology in Barcelona.
J Estrada*, N Andrew*, D Gibson, F Chang, F Gnad, J Gunawardena
"Cellular interrogation: exploiting cell-to-cell variability to discriminate regulatory mechanisms in oscillatory signalling"
PLoS Comput Biol 12:e1004995 2016. Full text PDF.
H Qi, S Prabakaran, F-C Cantrelle, B Chambraud, J Gunawardena, G Lippens, I Landrieu
"Characterization of neuronal tau protein as a target of extracellular-signal-regulated kinase"
J Biol Chem 291:7742-53 2016. PDF.
M Malleshaiah, M Padi, P Rué, J Quackenbush, A Martinez-Arias, J Gunawardena
"Nac1 coordinates a sub-network of pluripotency factors to regulate embryonic stem cell differentiation"
Cell Reports 14:1181-94 2016. Full text PDF.
2015
S L Field*, T Dasgupta*, H Bulsara, R S Savage, J Adebayo, M Cummings, J Gunawardena, N M Orsi
"Bayesian modelling suggests that IL-12 (p40), IL-13 and MCP-1 drive murine inflammatory networks in vivo"
BMC Syst Biol 9:76 2015. Full text PDF Amalgamated Additional Files.
J P Dexter*, T Dasgupta*, J Gunawardena
"Invariants reveal multiple forms of robustness in bifunctional enzyme systems"
Integr Biol 7:883-94 2015. PDF Cover Supplementary Mathematica notebook.
J P Dexter, P Xu, J Gunawardena, M N McClean
"Robust network structure of the Sln1-Ypd1-Ssk1 three-component phospho-relay prevents unintended activation of the HOG MAPK pathway in Saccharomyces cerevisiae"
BMC Syst Biol 9:17 2015. Full text PDF Supplementary Information.
2014
T Ahsendorf*, F Wong*, R Eils, J Gunawardena
"A framework for modelling gene regulation which accommodates non-equilibrium mechanisms"
BMC Biol, 12:102 2014. Full text PDF Additional File
BMC Biology commentary.
S Prabakaran*, M Hemberg*, R Chauhan*, D Winter, R Tweedie-Cullen, C Dittrich, E Hong, J Gunawardena, H Steen, G Kreiman, J A Steen
"Quantitative profiling of peptides from RNAs classified as non-coding"
Nat Commun doi:10.1038/ncomms6429 2014. Preview PDF Supplementary Information.
S Prabakaran, J Gunawardena, E Sontag
"Paradoxical results in perturbation-based biological network reconstruction"
Biophys J 106:2720-8 2014. PDF Supplementary Information.
J Gunawardena
"Models in biology: 'accurate descriptions of our pathetic thinking'". Invited review.
BMC Biol 12:29 2014. Full text PDF
Blog 
H1Connect Nature comment.
T Dasgupta*, D H Croll*, J A Owen*, M G Vander Heiden, J W Locasale, U Alon, L C Cantley, J Gunawardena
"A fundamental trade-off in covalent switching and its circumvention by enzyme bifunctionality in glucose homeostasis"
J Biol Chem, 289:13010-25 2014. PDF.
J Gunawardena
"Time-scale separation: Michaelis and Menten's old idea, still bearing fruit". Invited review.
FEBS J, 281:473-88 2014. PDF.
2013
I Mirzaev, J Gunawardena
"Laplacian dynamics on general graphs"
Bull Math Biol, 75:2118-49 2013. PDF.
N Hao, B A Budnik, J Gunawardena, E K O'Shea
"Tunable signal processing through modular control of transcription factor translocation"
Science, 339:460-4 2013. PDF
Editor's choice in Sci Signal and research highlight in Nat Rev Genet.
J P Dexter, J Gunawardena
"Dimerization and bifunctionality confer robustness to the isocitrate dehydrogenase regulatory system in Escherichia coli"
J Biol Chem, 288:5770-8 2013. PDF. Supplementary Mathematica notebook and accompanying Mathematica package.
2012
Y Xu, J Gunawardena
"Realistic enzymology for post-translational modification: zero-order ultrasensitivity revisited"
J Theor Biol, 311:139-52 2012. PDF.
R L Karp*, M Peréz Millán*, T Dasgupta*, A Dickenstein, J Gunawardena
"Complex-linear invariants of biochemical reaction networks"
J Theor Biol, 311:130-8 2012. PDF Supplementary information.
S Prabakaran, G Lippens, H Steen, J Gunawardena
"Post-translational modification: nature's escape from genetic imprisonment and the basis for dynamic information encoding"
WIREs Systems Biology and Medicine, 4:565-83 2012. PDF.
J Gunawardena
"A linear framework for time-scale separation in nonlinear biochemical systems"
PLoS ONE, 7:e36321 2012
The published version of this paper on the PLoS ONE site had typesetting and figure reference errors that were introduced by PLoS ONE during publication. These errors have finally been corrected in the online version and in the PDF. Supplementary information.
F Gnad, J. Estrada, J Gunawardena
"Proteus: a web-based, context-specific modelling tool"
Bioinformatics, 28:1284-6 2012. Full text PDF.
2011
S L Harvey, G Enciso, N E Dephoure, S P Gygi, J Gunawardena, D R Kellogg
"A phosphatase threshold sets the level of Cdk1 activity in early mitosis in budding yeast"
Mol Biol Cell, 22:3595-608 2011. Full text PDF.
S Prabakaran, R A Everley, I Landrieu, J-M Wieruszeski, G Lippens, H Steen, J Gunawardena
"Comparative analysis of Erk phosphorylation suggests a mixed strategy for measuring phospho-form distributions"
Mol Sys Biol, 7:482 2011. Full text PDF Supplementary Information
This was a featured paper in Molecular Systems Biology.
F Gnad, J Gunawardena, M Mann
"PHOSIDA 2011: the posttranslational modification database"
Nucleic Acids Res, 39:253-60 2011. PDF
This was a featured article in Nucleic Acids Research.
2010
F Gnad, F Forner, D F Zielinska, E Birney, J Gunawardena, M Mann
"Evolutionary constraints of phosphorylation in eukaryotes, prokaryotes and mitochondria"
Mol Cell Proteomics, 9:2642-53 2010. PDF.
2009
M. Thomson, J Gunawardena
"The rational parameterisation theorem for multisite post-translational modification systems"
J Theor Biol, 261:626-36 2009. PDF.
M Thomson, J Gunawardena
"Unlimited multistability in multisite phosphorylation systems"
Nature, 460:274-7 2009. doi:10.1038/nature08102. PDF Supplementary Information.
A Mallavarapu, M Thomson, B Ullian, J Gunawardena
"Programming with models: modularity and abstraction provide powerful capabilities for systems biology"
J Roy Soc Interface, 6:257-70 2009. full text PDF.
2008 and earlier
A K Manrai, J Gunawardena
"The geometry of multisite phosphorylation"
Biophys J, 95:5533-43 2008. PDF Supplementary Mathematica notebook.
N Andrew, D Craig, J P Urbanski, J Gunawardena, T Thorsen
"Microfluidic temporal cell stimulation"
Proceedings of the 12th International Conference on Miniaturized Systems for the Life Sciences, μTAS 2008. PDF.
J Gunawardena
"Signals and systems: towards a systems biology of signal transduction"
Invited paper for the Special Issue on Computational Systems Biology
Proc IEEE, 96:1386-97 2008. PDF.
J Gunawardena
"Distributivity and processivity in multisite phosphorylation can be distinguished through steady-state invariants"
Biophys J, 93:3828-34 2007. PDF.
J Gunawardena
"Multisite protein phosphorylation makes a good threshold but can be a poor switch"
PNAS 102:14617-22 2005. PDF.
M. Malleshaiah J Gunawardena
"Cybernetics redux: an outside-in strategy for unraveling cellular function"
Dev Cell 36:2-4 2016. PDF H1Connect
Preview of Mitchell, Wei & Lim, "Oscillatory stress stimulation uncovers Achilles' heel of the yeast MAPK signaling network", Science 350:1379-83 2015
J Gunawardena
"Beware the tail that wags the dog: informal and formal models in biology". Invited perspective.
Mol Biol Cell, 25:3441-4 2014. PDF.
J Gunawardena
"Biology is more theoretical than physics". Invited perspective.
Mol Biol Cell, 24:1827-9 2013. PDF.
J Gunawardena
"Silicon dreams of cells into symbols"
Nat Biotech 30:838-40 2012. PDF
News & Views on Karr et al, "A whole-cell computational model predicts phenotype from genotype", Cell 150:389-401 2012.
J Gunawardena
"Some lessons about models from Michaelis and Menten". Invited perspective.
Mol Biol Cell 23:517-9 2012. PDF.
J Gunawardena
"Biological systems theory"
Science 328:581-2 2010. PDF
News & Views on G Shinar, M Feinberg, "Structural sources of robustness in biochemical reaction networks", Science 327:1389-91 2010.
G Lippens, J Gunawardena, I Landrieu, C Smet-Nocca, S Prabakaran, B Parent, A Leroy, I Huvent
"Post-translational modifications of the proteome: the example of tau in the neuron and the brain"
In J Loscalzo, A-L Barabási, E K Silverman (editors), Network Medicine. Complex Systems in Human Disease and Therapeutics, Harvard University Press, Cambridge MA USA, 2017. HUP.
J Gunawardena
"Models in systems biology: minimalist versus exhaustive strategies"
In B Engquist (editor), Encyclopedia of Applied and Computational Methods, Springer-Verlag, Berlin, Germany, 2015. Springer.
J Gunawardena
"Modeling of interaction networks in the cell: theory and mathematical methods"
In H Weinstein (editor), Simulation and Modeling, pages 243-67. Volume 9 of E Egelman (editor), Comprehensive Biophysics, Academic Press, Oxford. 2012. Elsevier.
J Gunawardena
"Models in systems biology: the parameter problem and the meanings of robustness"
In H. Lodhi, S. Muggleton (editors), Elements of Computational Systems Biology, John Wiley and Sons, New York, 2010. PDF.
Yen-Der Li
"Cell density affects Erk signaling heterogeneity"
Summer research presentation, 2013. PDF.
J Gunawardena
"A linear elimination framework"
Preprint, 2011. q-bio.MN:1109.6231.
M Thomson, J Gunawardena
"Multi-bit information storage by multisite phosphorylation"
Preprint, 2007. q-bio.MN:0706.3735.
A Mallavarapu, M Thomson, B Ullian, J Gunawardena
"Modular model building"
Preprint, 2007. q-bio.MN:0710.3421.
M Lipson
"Differential and graphical approaches to multistability for chemical reaction networks"
Senior Honours Thesis, Hoopes Prize, 2007. q-bio.MN:0709.0125.
J Gunawardena
"Chemical Reaction Network Theory for in-silico biologists"
Preprint, 2003. PDF.
J Gunawardena
"Notes on Metabolic Control Analysis"
Preprint, 2002. PDF.
C J DeHart, L Fornelli, L C Anderson, J W Sikora, D Agarwal, D Lu, P D Compton, C L Hendrickson, P M Thomas, G Lahav, J Gunawardena, N L Kelleher
"A multi-modal proteomics strategy for characterizing in vitro p53 modforms"
American Society for Mass Spectrometry (ASMS) Annual Conference, Indianopolis, Indiana, June 2017. Poster.
C J DeHart, L Fornelli, O S Skinner, L C Anderson, P D Compton, C L Hendrickson, P M Thomas, G Lahav, J Gunawardena, N L Kelleher
"Mapping p53 proteoforms by native and denaturing top-down mass spectrometry"
American Society for Mass Spectrometry (ASMS) Annual Conference, San Antonio, Texas, June 2016. Poster.
M Malleshaiah, M Padi, P Rue, J Quackenbush, A Martinez-Arias, J Gunawardena
"Nac1 coordinates a sub-network of pluripotency factors to regulate embryonic stem cell differentiation"
International Society for Stem Cell Research Conference, San Francisco, June 2016. Poster.
Gunawardena Lab
"Cellular information processing", Harvard Undergraduate Life Sciences Research Fair, 2016. Poster.
M Cummings, T Dasgupta, J Adebayo, G Mappa, R Hutson, N Wilkinson, J Gunawardena, N M Orsi
"Cytokine networks in endometrial carcinogenesis"
UK Pathological Society, Dublin, Ireland, June 2015. Poster
Awarded 2nd prize by the UK Pathological Society.