MRC Laboratory of Molecular Biology
Hills Rd
Cambridge CB20QH
United Kingdom
email: danielh@mrc-lmb.cam.ac.uk
phone: +44 (0) 1223 40 2254
I am mainly interested in the mechanisms and statistics of transcriptional regulation in metazoan cells. Several questions are important in this respect:
What is the interplay of epigenetic modifications and gene expression?
How does the cell cope with the problems of 'low-molecule-numbers' statistics?
How does a cell reorganize its transcriptional network upon differentiation?
To answer these questions, I am pursuing a systems-biology approach based on accurate experimental quantification with next-generation sequencing technologies such as mRNA-seq and ChIP-seq, studying cell population diversity with flow cytometry, and statistical and mathematical analysis of the data.
My studies are focused on the system of murine T helper cells, particularly the Th2 subtype, which provides a valuable model for mammalian cell differentiation and is experimentally accessible.
The figure on the right (Hebenstreit et al, Nucleic Acids Res, 2011) provides an example of how the combination of genome-wide assays such as microarrays and ChIP-seq visualizes patterns, thereby indicating the biological mechanism:
The heatmap shows the gene expression (on the y-axis) and activating histone modification (as normalized locus specific chromatin status, NLCS, on the x-axis) levels for all genes in a murine Th2 cell. The structure clearly reveals two main groups of genes, lowly expressed ones without activating histone marks, and highly expressed ones with activating histone marks. This suggests a fundamental switch-like mechanism underlying transcriptional regulation.
1. Hebenstreit D*, Deonarine A*, Babu MM, Teichmann SA.
Duel of the fates: the role of transcriptional circuits and noise in CD4+ cells.
Current Opinion in Cell Biology. 2012. in press.
2. Brookes E*, de Santiago I*, Hebenstreit D, Morris KJ, Carroll T, Xie SQ, Stock JK, Heidemann M, Eick D, Nozaki N, Kimura H, Ragoussis J, Teichmann SA, Pombo A.
Polycomb associates genome-wide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs.
Cell Stem Cell. 2012 Feb;10(2):157-70. Featured article.
3. Hebenstreit D, Fang M, Gu M, Charoensawan V, van Oudenaarden A, Teichmann SA.
RNA sequencing reveals two major classes of gene expression levels in metazoan cells.
Molecular Systems Biology. 2011 Jun;7:497. Featured article.
4. Hebenstreit D, Teichmann SA.
Analysis and simulation of gene expression pro files in pure and mixed cell populations.
Phys Biol. 2011 Jun;8(3):035013.
5. Hebenstreit D, Gu M, Haider S, Turner DJ, Lio' P, Teichmann SA.
EpiChIP: Gene-by-gene quanti fication of epigenetic modi cation levels.
Nucleic Acids Res. 2011 Mar;39(5):e27. Featured article.
6. Maier E, Hebenstreit D, Posselt G, Hammerl P, Duschl A, Horejs-Hoeck J.
Inhibition of suppressive T cell factor 1 (TCF-1) isoforms in naive CD4+ T cells is mediated by IL-4/STAT6 signaling.
J Biol Chem. 2011 Jan;286(2):919-28.
7. Hebenstreit D, Giaisi M, Treiber MK, Zhang XB, Mi HF, Horejs-Hoeck J, Andersen KG, Krammer PH, Duschl A, Li-Weber M.
LEF-1 negatively controls interleukin-4 expression through a proximal promoter regulatory element.
J Biol Chem. 2008 Aug;283(33):22490-7.
8. Maier E, Wirnsberger G, Horejs-Hoeck J, Duschl A, Hebenstreit D.
Identi fication of a distal tandem STAT6 enhancer element within the CCL17 locus.
Hum Immunol. 2007 Dec;68(12):986-92.
9. Wirnsberger G, Hebenstreit D, Posselt G, Horejs-Hoeck J, Duschl A.
IL-4 induces expression of TARC/CCL17 via two STAT6 binding sites.
Eur J Immunol. 2006 Jul;36(7):1882-91.
10. Hebenstreit D, Wirnsberger G, Horejs-Hoeck J, Duschl A.
Signaling mechanisms, interaction partners, and target genes of STAT6.
Cytokine Growth Factor Rev. 2006 Jun;17(3):173-88.
11. Hebenstreit D, Ferreira F.
Structural changes in calcium-binding allergens: use of circular dichroism to study binding characteristics.
Allergy. 2005 Sep;60(9):1208- 11.
12. Hebenstreit D, Horejs-Hoeck J, Duschl A.
JAK/STAT-dependent gene regulation by cytokines.
Drug News Perspect. 2005 May;18(4):243-9.
13. Hebenstreit D, Luft P, Schmiedlechner A, Duschl A, Horejs-Hoeck J.
SOCS-1 and SOCS-3 inhibit IL-4 and IL-13 induced activation of Eotaxin-3/CCL26 gene expression in HEK293 cells.
Mol Immunol. 2005 Feb;42(3):295-303.
14. Hebenstreit D, Luft P, Schmiedlechner A, Regl G, Frischauf AM, Aberger F, Duschl A, Horejs-Hoeck J.
IL-4 and IL-13 induce SOCS-1 gene expression in A549 cells by three functional STAT6-binding motifs located upstream of the transcription initiation site.
J Immunol. 2003 Dec 1;171(11): 5901-7.
15. Wopfner N, Willeroidee M, Hebenstreit D, van Ree R, Aalbers M, Briza P, Thalhamer J, Ebner C, Richter K, Ferreira F.
Molecular and immunological characterization of pro filin from mugwort pollen.
Biol Chem. 2002 Nov;383(11):1779-89.
Scientific:
EpiChIP software
Faculty of 1000
Non-scientific:
Sunday Morning Breakfast Cereal Comics
Abstruse Goose Cartoons
xkcd Cartoons
Cambridge University Ice Hockey Club