Juliane Liepe

I moved to the Max-PLanck-Institute for bio[physical Chemistry in Goettingen, where I started my new research group Quantitative and Systems Biology.

I am currently guest researcher in the Theoretical Systems Biology group after completing an NC3Rs David Sainsbury Fellowship.

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In vivo Immune Cell Migration

Research Background Publications Software Projects Books Patent Conferences and Seminars

 

Research interests

Cell migration during the innate and adaptive immune response

I am studying signalling processes that are related to the immune response, with a focus on the innate immune response. After an injury, parts of the immune system are activated, specific immune cell leave the blood vessels and migrate through the tissue to the side of the injury. I investigate the migration of these immune cells, more specifically macrophages and neutrophils, which are the first layer of defence of the immune system in humans. It is still not fully understood, which signals drive these cells towards the injury, how these cells migrate and what do these cells do once they reached the site of injury.
To answer these questions I use an integrative approach, combining mathematical modelling and in vivo imaging studies. As a result I am developing diverse in silico tools to understand immune cell signalling.

 

Proteasome as a regulator of the immune response

The proteasome is a molecular machine that degrades proteins. The majority of epitopes presented through the MHC class I pathway are generated by the proteasome, which highlights its role in the adaptive immune response. Furthermore, there is increasing evidence that the proteasome regulates and is regulated by the production of cytokines and chemokines.
I use mathematical and bioinformatics tools to study the catalysis processes of different proteasome isoforms and their resulting impact on the regulation of the immune response in health and disease.


 

Background

I studied Biochemistry (2004-2008) at the University of Potsdam (Germany). During this time I also studied two years of Mathematics. During my University education I was a research assistant in the group of Non-linear Dynamics (University Potsdam, Germany) under supervision of Professor Juergen Kurths and in the Protein Biochemistry group (Universitaetsmedizin Charite Berlin, Germany) under supervision of Professor Peter M Kloetzel.
In 2009 I joint the 1+3 years Welcome Trust PhD program at Imperial College London, which started with a MSc in Bioinformatics and theoretical Systems Biology. I did my PhD under supervision of Professor Michael PH Stumpf on the topic “Novel descriptive and model based statistical approaches in immunology and signal transduction”.
After completing my PhD I was awarded the NC3Rs David Sainsbury research fellowship.


 

Publications

2016:
A large fraction of HLA class I ligands are proteasome-generated spliced peptides.
Liepe J, Marino F, Sidney J, Jeko A, Bunting DE, Sette A, Kloetzel PM, Stumpf MPH, Heck AJR and Mishto M
Science. 2016 October. DOI: 10.1126/science.aaf4384
Free access to this Science publication via the following links only: abstract | reprint | fulltext

Systems analysis of the dynamic inflammatory response to tissue damage reveals spatio-temporal properties of the wound attractant gradient.
Weavers H*, Liepe J*, Sim A, Wood W, Martin P and Stumpf MPH
Current Biology. 2016 July. DOI: http://dx.doi.org/10.1016/j.cub.2016.06.012

Accurate reconstruction of cell and particle tracks from 3D live imaging data.
Liepe J*, Sim A*, Weavers H, Ward L, Martin P and Stumpf MPH
Cell Systems. 2016 July. DOI: http://dx.doi.org/10.1016/j.cels.2016.06.002

CD8+ T cells of Listeria monocytogenes‐infected mice recognize both linear and spliced proteasome products.
Platteel ACM, Mishto M, Textoris-Taube K, Keller C, Liepe J, Busch DH, Kloetzel PM and Sijts AJAM
Eur J Immunol. 2016 Mar 16;doi: 10.1002/eji.201545989.

2015:

The T210M substitution in the HLA-A*02:01 gp100 epitope strongly affects overall proteasomal cleavage site usage and antigen processing.
Textoris-Taube K, KellerC , Liepe J, Henklein P, Sidney J, Sette A, Kloetzel PMK and Mishto M.
Journal of Biological Chemistry (JBC). 2015 Oct 27;doi: 10.1074/jbc.M115.695189.

Quantitative time-resolved analysis reveals intricate, differential regulation of standard- and immuno-proteasomes.
Liepe J, Holzhütter HG, Bellavista E, Kloetzel PM, Stumpf MPH and Mishto M.
elife. 2015 Sep 22;4. doi: 10.7554/eLife.07545.

Inference of random walk models to describe leukocyte migration.
Jones PJM, Sim A, Taylor HB, Bugeon L, Dallman JM, Pereira B, Stumpf MPH and Liepe J.
Phys Biol. 2015 Sep 25;12(6):066001. doi: 10.1088/1478-3975/12/6/066001.

Goldstein-Kac telegraph processes with random speeds: Path probabilities, likelihoods, and reported Lévy flights.
Sim A, Liepe J and Stumpf MPH.
Phys. Rev. E 2015 Apr 15. doi: 10.1103/PhysRevE.91.042115.

2014:

Proteasome isoforms exhibit only quantitative differences in cleavage and epitope generation.
Mishto M, Liepe J, , Textoris-Taube K, Keller C, Henklein P, Weberruß M, Dahlmann B, Enenkel C, Voigt A, Kuckelkorn U, Stumpf MP, Kloetzel PM.
Eur J Immunol. 2014 Sep 17. doi: 10.1002/eji.201444902.

Modeling proteasome and proteasome regulator activities.
Liepe J, Holzhütter H-G, Kloetzel PM, Stumpf MPH, Mishto M
Biomolecules 2014, 4(2), 585-599; doi:10.3390/biom4020585.

Information Theory and Signal Transduction Systems: From Molecular Information Processing to Network Inference.
Mc Mahon S, Aaron Sim A, Filippi S, Johnson R, Liepe J, Smith D, Stumpf MPH
Seminars in Cell and Developmental Biology 2014, DOI: 10.1016/j.semcdb.2014.06.011

A Framework for Parameter Estimation and Model Selection From Experimental Data in Systems Biology Using Approximate Bayesian Computation.
Liepe J, Kirk P, Filippi S, Toni T, Stumpf MPH
Nature Protocols 2014 Jan; 9: 439–456. doi:10.1038/nprot.2014.025.

2013:

Maximizing the Information Content of Experiments in Systems Biology.
Liepe J, Filippi S, Komorowski M, Stumpf MPH
PLoS Comput Biol. 2013 Jan;9(1):e1002888. doi: 10.1371/journal.pcbi.1002888. Epub 2013 Jan 31.

p38 and JNK have opposing effects on persistence of in vivo leukocyte migration in zebrafish.
Taylor HB *, Liepe J *, Barthen C, Bugeon L, Huvet M, Kirk PD, Brown SB, Lamb JR, Stumpf MP, Dallman MJ
Immunol Cell Biol. 2013 Jan;91(1):60-9. doi: 10.1038/icb.2012.57. Epub 2012 Nov 20.

until 2012:

Calibrating spatio-temporal models of leukocyte dynamics against in vivo live-imaging data using approximate Bayesian computation.
Liepe J, Taylor H, Barnes CP, Huvet M, Bugeon L, Thorne T, Lamb JR, Dallman MJ, Stumpf MP.
Integr Biol (Camb). 2012 Mar;4(3):335-45. doi: 10.1039/c2ib00175f. Epub 2012 Feb 10.

GPU accelerated biochemical network simulation.
Zhou Y, Liepe J, Sheng X, Stumpf MP, Barnes C.
Bioinformatics. 2011 Mar 15;27(6):874-6. doi: 10.1093/bioinformatics/btr015. Epub 2011 Jan 11.

ABC-SysBio–approximate Bayesian computation in Python with GPU support.
Liepe J, Barnes C, Cule E, Erguler K, Kirk P, Toni T, Stumpf MP.
Bioinformatics. 2010 Jul 15;26(14):1797-9. doi: 10.1093/bioinformatics/btq278.

The 20S proteasome splicing activity discovered by SpliceMet.
Liepe J, Mishto M, Textoris-Taube K, Janek K, Keller C, Henklein P, Kloetzel PM, Zaikin A.
PLoS Comput Biol. 2010 Jun 24;6(6):e1000830. doi: 10.1371/journal.pcbi.1000830.

* These authors contributed equally to this work

 

Peer Reviewed Conference Proceedings

Microtubule tracking from stochastic optical reconstruction microscopy images.
J. Liepe, F. Felizzi, A. Pernus and M. Hanulova
Proceedings of the 8th WCSB, 2011

Variety of dynamical regimes in a population of coupled synthetic genetic oscillators.
A. Koseska, A. Zaikin, J. Liepe, and J. Kurths
Proceedings of the 3rd International Conference “Physics and Control” (PhysCon), 2007


 

Software Projects

ABC-SysBio : A tool for parameter inference and model selection.


 

Book Chapters

ABC in Systems Biology.
J. Liepe and MPH Stumpf.
Handbook of Approximate Bayesian Computation, Taylor and Francis, (in press)

Inference of signalling pathway models.
T. Toni, J. Liepe and M.P.H. Stumpf.
Handbook of Statistical Systems Biology, Wiley, 2011


 

Patent

“Method for identification of proteasome generated spliced peptides”. 2010,
Application number: EP10075087.6. Application date: 25.02.2010. Applicant: Charité – Berlin.


 

Invited talks at Conferences and Seminars

“From in silico to the clinic: methods to study proteasome-catalysed peptide splicing”. 2017,
Departmental Seminar at Department of Cell Biology, Harvard Medical School
Boston (MA), US

“Proteasome-catalysed peptide splicing and its biological implication”. 2017,
RAGON Seminar series at the Ragon Institute of MGH, MIT & Harvard
Cambridge (MA), US

“From in silico to the clinic: methods to study proteasome-catalysed peptide splicing”. 2017,
Seminar at the De Duve Institute
Brussels, Belgium

“Dynamics of Proteasome-catalysed peptide splicing – curse or novel therapeutic possibilities?”. 2016,
Seminar at Max Planck Institute for Biophysical Chemistry
Goettingen, Germany

“From in silico to the clinic: methods to study proteasome-catalysed peptide splicing”. 2016,
Seminar at the Ludwig Institute for Cancer Research
Oxford, UK

“Computational models as microscopes: rate-limiting steps in proteasomes”. 2016,
Plenary speaker at Quantitative Systems Pharmacology UK
Surrey, UK

“Computational models as microscopes: Dynamics of standard- and immuno-proteasome regulate the human immune response”. 2015,
Keynote talk at the 6th annual Symposium on “Computational Biology & Innovation” at University College Dublin
Dublin, Ireland

“Bayesian Methods to study Immune Cell Migration”. 2015,
Seminar at the Institute for Biochemistry and Biology of the University of Potsdam
Potsdam, Germany

“Rate-limiting steps in standard- and immuno-proteasomes”. 2015,
Seminar at the Centre for Mathematical Medicine and Biology of the University of Nottingham
Nottingham, UK

“Computational models as microscopes: rate-limiting steps in proteasomes”. 2015,
Bijvoet Seminar at Utrecht University
Utrecht, The Netherlands

“Signalling pathways of leukocyte migration in silico”. 2015,
3Rs seminar at Imperial College London
London, UK

“Computational models as microscopes: rate-limiting steps in proteasomes”. 2015,
CISBIO Crick & Jaroslav Stark Lecture ( Modelling from Structures to Systems),
London, UK

“An ABC framework to calibrate models of leukocyte dynamics”. 2014,
NIPS (Neural Information Processing Systems Foundation),
Montreal, Canada

“Untangling proteasome proteolysis – Key steps toward the systems biology of the immune system”. 2014,
CNR (Consiglio Nazionale delle Ricerche),
Rome, Italy

“Calibrating multi-scale models of macrophage dynamics”. 2011,
PICA (Physics of Immunity: Complexity Approach),
Dresden, Germany.

 

Conferences

Oral presentation
“Moving towards understanding of leukocyte migration”. 2013,
ICMS (Stochastic, statistical and computational approaches in Immunology),
Edinburg, UK

Oral presentation
“Bayesian experimental design to probe cellular decision making processes”. 2012,
MASAMB (Workshop on Mathematical & Statistical Aspects of Molecular Biology),
Berlin, Germany

Oral presentation
“Quantitative imaging reveals p38 MAP kinase mediated chemotactic variability in leukocytes”. 2010,
MASAMB (Mathematical and Statistical Aspects of Molecular Biology),
University of Warwick, UK.

Poster presentation
EMBO Workshop on Visualizing Biological Data, 2010
Heidelberg, Germany

Poster presentation
International Symposium for Topical Problems of Biophotonics,2009
Nichninovgorod, Russia.