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Theoretical Immunology

Monday 7 October 2013



Prof. dr. Rob J. de Boer
Theoretical Biology & Bioinformatics








Curriculum Vitae
Majoring in Computational Biology Rob J. de Boer studied at Utrecht University, where he received his Ph.D. in 1989 (cum laude, with Paulien Hogeweg) in Theoretical Immunology. As a postdoctoral fellow he worked at the Los Alamos National Laboratory (with Alan Perelson). In 1991 he started his own research group at the Department of Biology at Utrecht University, and was awarded the prestigious NWO VICI award in 2004. He became group leader in 2009, and has been a member of the external faculty of the Santa Fe Institute since 1992.

Research summary
The immune system is a fascinating complex system taking decisions on how to respond to a wide variety of stimuli, varying from lethal pathogens to harmless proteins in the food. Decisions are remembered for life in the form of immunological memory. Most of the research in immunology is of a qualitative nature, describing novel cell types, molecules, and genes. The proper understanding of such a complex systems also requires a more quantitative approach describing the various population sizes, the turnover rates of the cells within each population, their migration rates, and the rates at which cells form contacts with other cells.

A major part of our work is to develop a more quantitative immunology by describing the population dynamics of its major populations using a variety of labeling techniques and mathematical modeling to analyze the data. Using deuterium labeling we estimate the expected life span of naïve and memory T cells in volunteers and HIV infected patients, finding that long-lived immunological memory is maintained by short-lived cells, and that HIV infecting increases cellular turnover rates. We aim to quantify the daily number of target cells that one cytotoxic T cell can kill per day.

Using a variety of modeling techniques we analyze 2-photon microscopy data to quantify the migration of T cells in lymphoid tissue and within the skin of mice. We estimate the true long contact times required to stimulated naïve T cells from short videos, and find evidence for directed migration of cytotoxic T cells in peripheral tissues.

Pathogens are also fascinating complex systems that by their faster evolution manage to exploit properties of the immune system to elicit inappropriate immune reactions. We study host-pathogen evolution by in silico evolution models. We study the evolution of polymorphism in the antigen presentation pathway and of the KIR molecules on natural killer cells. Recently we started to study the evolution and epidemiology of pathogens that are adapting each unique immune system of their massively heterogeneous hosts.

For more information, visit the website at http://theory.bio.uu.nl/rdb

Lab members

Postdocs
Johannes Textor
Leila Peirie
Aridaman Pandit
Julia Drylewicz (see http://theory.bio.uu.nl)

Ph.D. students
Paola Carrilo Bustamante
Sai Gadhamsetty
Ioana Niculescu
Chris van Dorp
Rutger Woolthuis
Bram Gerritsen (see http://theory.bio.uu.nl)

Publications
Naik S.H., Perie L., Swart E., Gerlach C., Van Rooij N., De Boer R.J. & Schumacher T.N. (2013). Diverse and heritable lineage imprinting of early haematopoietic progenitors. Nature, 496: 229-232.

Gerlach C., Rohr J.C., Perie L., Van Rooij N., Van Heijst J.W., Velds A., Urbanus J., Naik S.H., Jacobs H., Beltman J.B., De Boer R.J. & Schumacher T.N. (2013). Heterogeneous differentiation patterns of individual CD8+ T cells. Science, 340: 635-639.

De Boer RJ. Which of our modeling predictions are robust? PLoS Comput Biol.2012 Jul;8(7):e1002593. Epub 2012 Jul 26. PubMed PMID: 22844235; PubMed Central PMCID: PMC3405990.

den Braber I, Mugwagwa T, Vrisekoop N, Westera L, Mogling R, de Boer AB, Willems N, Schrijver EH, Spierenburg G, Gaiser K, Mul E, Otto SA, Ruiter AF, Ackermans MT, Miedema F, Borghans JA, de Boer RJ, Tesselaar K. Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans. Immunity. 2012 Feb 24;36(2):288-97. PubMed PMID: 22365666.

Beltman JB, Allen CD, Cyster JG, de Boer RJ. B cells within germinal centers migrate preferentially from dark to light zone. Proc Natl Acad Sci U S A. 2011 May 24;108(21):8755-60. Epub 2011 May 9. PubMed PMID: 21555569; PubMed Central PMCID: PMC3102384.