Prof. Dr. Rob J. de Boer
Theoretical Biology & Bioinformatics
Faculty of Science, Utrecht University
Kruytgebouw, room Z505
3584 CH Utrecht
Tel. +31-(0)30-253 7560
Fax +31-(0)30-253 3655
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.
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://tbb.bio.uu.nl/rdb
Chris van Dorp
Asquith, Becca & de Boer, Rob J (16-12-2016). How lymphocytes add up. Nature Immunology, 18 (1), (pp. 12-13) (2 p.).
Gadhamsetty, Saikrishna, Coorens, Tim & de Boer, Rob J (2016). Notwithstanding circumstantial alibis, cytotoxic T cells can be major killers of HIV-1 infected cells. Journal of Virology, 90 (16), (pp. 7066-7083).
Gerritsen, Bram, Pandit, Aridaman, Andeweg, Arno C & de Boer, Rob J (2016). RTCR – a pipeline for complete and accurate recovery of T cell repertoires from high throughput sequencing data. Bioinformatics, 32 (20), (pp. 3098-3106) (9 p.).
Carrillo-Bustamante, Paola, Kesmir, C. & de Boer, Rob J (2016). The evolution of natural killer cell receptors. Immunogenetics, 68 (1), (pp. 3-18).
Textor, Johannes, Mandl, Judith N & de Boer, Rob J (2016). The Reticular Cell Network – A Robust Backbone for Immune Responses. PLoS Biology, 14 (10).
Carrillo-Bustamante, Paola, Kesmir, C. & de Boer, Rob J (2015). A Coevolutionary Arms Race between Hosts and Viruses Drives Polymorphism and Polygenicity of NK Cell Receptors. Molecular Biology and Evolution, 32 (8), (pp. 2149-2160) (12 p.).
Carrillo-Bustamante, Paola, Kesmir, Can & de Boer, Rob J (2015). Can Selective MHC Downregulation Explain the Specificity and Genetic Diversity of NK Cell Receptors?. Frontiers in Immunology, 6, (pp. 311).
Niculescu, Ioana, Textor, Johannes & de Boer, Rob J (2015). Crawling and Gliding – A Computational Model for Shape-Driven Cell Migration. PLoS Computational Biology, 11 (10) (22 p.).
Pandit, Aridaman & de Boer, Rob J (2015). HIV-1 CCR5 gene therapy will fail unless it is combined with a suicide gene. Scientific Reports, 5.
Saeki, Koichi, Doekes, Hilje M. & De Boer, Rob J. (01-06-2015). Optimal T cell cross-reactivity and the role of regulatory T cells. Journal of Theoretical Biology, 375, (pp. 4-12) (9 p.)
Gadham Setty, S., Beltman, Joost B. & de Boer, Rob J. (01-11-2015). What do mathematical models tell us about killing rates during HIV-1 infection?. Immunology Letters, 168 (1), (pp. 1-6) (6 p.).
Gadham Setty, S., Marée, Athanasius F M, Beltman, Joost B & de Boer, Rob J (15-04-2014). A general functional response of cytotoxic T lymphocyte-mediated killing of target cells. Biophysical Journal, 106 (8), (pp. 1780-1791) (12 p.).
van Dorp, Christiaan H, van Boven, Michiel & de Boer, Rob J (2014). Immuno-epidemiological modeling of HIV-1 predicts high heritability of the set-point virus load, while selection for CTL escape dominates virulence evolution. PLoS Computational Biology, 10 (12), (pp. e1003899).
Carrillo-Bustamante, Paola, Kesmir, Can & de Boer, Rob J. (01-01-2014). Quantifying the Protection of Activating and Inhibiting NK Cell Receptors during Infection with a CMV-Like Virus. Frontiers in Immunology, 5 (14 p.).
Pandit, Aridaman & de Boer, Rob J (2014). Reliable reconstruction of HIV-1 whole genome haplotypes reveals clonal interference and genetic hitchhiking among immune escape variants. Retrovirology, 11 (56) (15 p.).
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<sup>+</sup> 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.