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Department of Biochemistry

 
Jussi Taipale

Transcriptional control of growth.

 

Decades of work by biological scientists have revealed many fundamental mechanisms of life, yet several questions remain unanswered. This is in part because they are difficult to study using established methods and technologies that mainly analyse or model behaviour of few molecules in isolation or the effect of loss of one or a few genes on cellular or organismal functions. The principal aim of the Taipale Group is to understand two systems-level questions that are presently poorly understood: the mechanisms that control growth of tissues and organisms, and the rules that specify how DNA sequence determines when and where genes are expressed.

 

Research objectives

  • Identify mechanisms that govern transcription factor binding in vitro and in live cells.

  • Use the resulting information to understand how DNA sequence determines when and where genes are expressed.

  • Build a model of gene regulatory networks that control growth, and validate the model's predictions using reverse genetics in cultured cells and in model organisms.

 

Key publications

de Boer CG, Taipale J (2023). Hold out the genome: a roadmap to solving the cis-regulatory code. Nature, Dec 13 2023. doi: 10.1038/s41586-023-06661-w

Sahu B, Hartonen T, Pihlajamaa P, Wei B, Dave K, Zhu F, Kaasinen E, Lidschreiber K, Lidschreiber M, Daub CO, Cramer P, Kivioja T, Taipale J (2022). Sequence determinants of human gene regulatory elements. Nature Genetics, 54(3):283-294. doi: 10.1038/s41588-021-01009-4

Dave K, Sur I, Yan J, Zhang J, Kaasinen E, Zhong F, Blaas L, Li X, Kharazi S, Gustafsson C, De Paepe A, Månsson R, Taipale J (2017). Mice deficient of Myc super-enhancer region reveal differential control mechanism between normal and pathological growth. eLife, 6:e23382. doi: 10.7554/eLife.23382

Yin Y, Morgunova E, Jolma A, Kaasinen E, Sahu B, Khund-Sayeed S, Das PK, Kivioja T, Dave K, Zhong F, Nitta KR, Taipale M, Popov A, Ginno PA, Domcke S, Yan J, Schübeler D, Vinson C, Taipale J (2017). Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science, 356(6337):eaaj2239. doi: 10.1126/science.aaj2239

Zhu F, Farnung L, Kaasinen E, Sahu B, Yin Y, Wei B, Dodonova SO, Nitta KR, Morgunova E, Taipale M, Cramer P, Taipale J (2018). The interaction landscape between transcription factors and the nucleosome. Nature, 562(7725):76-81. doi: 10.1038/s41586-018-0549-5

Haapaniemi E, Botla S, Persson J, Schmierer B, Taipale J (2018). CRISPR-Cas9 genome editing induces a p53-mediated DNA damage response. Nat. Med., 24(7):927-930. doi: 10.1038/s41591-018-0049-z

Morgunova E, Yin Y, Das PK, Jolma A, Zhu F, Popov A, Xu Y, Nilsson L, Taipale J (2018). Two distinct DNA sequences recognized by transcription factors represent enthalpy and entropy optima. eLife, 7:e32963. doi: 10.7554/eLife.32963

Contact details

Personal Assistant  Karen Condie (Personal Assistant)

Telephone  +44 (0)1223 333498

Email  pataipale@bioc.cam.ac.uk

Location  Sanger Building

Opportunities

The Taipale Group is accepting enquiries from prospective interns, undergraduate students, postgraduate students and postdoctoral researchers.