GROUP LEADER: Luis Serrano (ICREA Research Professor)

STAFF SCIENTISTS: Martin Schieffer (until summer 2018), Maria Lluch

POSTDOCTORAL FELLOWS: Eva Yus (until Septmber 2018), Raul Burgos, Carlos Pinero, Claire Lastrucci, Sarah di Bartolo, Leandro Radutsky, Marc Weber, Jae Seong Yang (until July 2018)

PhD STUDENTS: Daniel Shaw, Samuel Miravet, Ariadna Montero, Hannah Benisty

TECHNICIANS: Sira Martinez, Toni Ferrar, Violeta Beltran,

BIOINFORMATICIANS: Javier Delgado, Damiano Cianferoni (since September 2018)

PROGRAMMER: Anas Gharrab (since 2018)

SUMMARY

Our group is interested in the quantitative understanding and rational engineering of living systems (ranging from gene networks to organisms). For this purpose, we use a combination of tools that involve software for protein design and simulations of networks and experimental approaches. Our approach is based on first understanding a system and then engineering it to obtain the properties we want.  Our philosophy is also whenever possible identifying the possible practical applications for human health and biotechnology of our work.

Systems level expression correlation of Ras-like GTPase regulators and dysregulation in cancer. Spearman’s rank correlations for the Ras superfamily and their GEF and GAP regulators in normal adult tissues and organs. (a) Schematic diagram of the Ras superfamily of small GTPases that cycle between a GDP-bound “OFF-state” and a GTP-bound “ON-state”. This cycling is regulated by GEF and GAP proteins. (b) Number of Ras superfamily and regulators genes in four species (homo sapiens, hs; mus musculus, mm; dr, danio rerio, dr; drosophila melanogaster, dm). (c) Schematic figure of protein and gene expression datasets used and main data analyses performed in this study. (d) Spearman’s rank correlation values of the RAS vs GEF, RAS vs GAP, and the GEF vs GAP for the four subfamilies displayed as a heat map (normal tissue datasets dmNT_01, ggNT_01, oaNT, mdNT_01, mmNT_01, mmNT_02, mmuNT_01, ppyNT_01, ptNT_01, ppNT_01, ggoNT_01, hsNT_01, hsNT_02, hsNT_03, hsNT_04, hsNT_05).

Fig. 01

Systems level expression correlation of Ras-like GTPase regulators and dysregulation in cancer. Spearman’s rank correlations for the Ras superfamily and their GEF and GAP regulators in normal adult tissues and organs. (a) Schematic diagram of the Ras superfamily of small GTPases that cycle between a GDP-bound “OFF-state” and a GTP-bound “ON-state”. This cycling is regulated by GEF and GAP proteins. (b) Number of Ras superfamily and regulators genes in four species (homo sapiens, hs; mus musculus, mm; dr, danio rerio, dr; drosophila melanogaster, dm). (c) Schematic figure of protein and gene expression datasets used and main data analyses performed in this study. (d) Spearman’s rank correlation values of the RAS vs GEF, RAS vs GAP, and the GEF vs GAP for the four subfamilies displayed as a heat map (normal tissue datasets dmNT_01, ggNT_01, oaNT, mdNT_01, mmNT_01, mmNT_02, mmuNT_01, ppyNT_01, ptNT_01, ppNT_01, ggoNT_01, hsNT_01, hsNT_02, hsNT_03, hsNT_04, hsNT_05).

RESEARCH PROJECTS

  1. Quantitative understanding and whole-cell modelling of a whole organism: M pneumoniae
  2. Engineering of M. pneumoniae to treat human diseases.
  3. Quantitative understanding of cellular processes in humans and its role in disease

SELECTED PUBLICATIONS

Carleton LA, Chakravarthy R, van der Sloot AM, Mnich K, Serrano L, Samali A and Gorman AM.
“Generation of rationally-designed nerve growth factor (NGF) variants with receptor specificity.”
Biochem Biophys Res Commun, 495(1):700-705, 2018.

Besray Unal E, Kiel C, Benisty H, Campbell A, Pickering K, Bluthgen N, Sansom OJ and Serrano L.
“Systems level expression correlation of Ras GTPase regulators.”
Cell Commun Signal, 16(1): 46, 2018.

Blanco JD, Radusky L, Climente-Gonzalez H and Serrano L.
“FoldX accurate structural protein-DNA binding prediction using PADA1 (Protein Assisted DNA Assembly 1).”
Nucleic Acids Res, 46(8):3852-3863, 2018.

Carleton LA, Chakravarthy R, van der Sloot AM, Mnich K, Serrano L, Samali A and Gorman AM.
“Generation of rationally-designed nerve growth factor (NGF) variants with receptor specificity.”
Biochem Biophys Res Commun, 495(1):700-705, 2018.

Dmitrijeva M, Ossowski S, Serrano S and Schaefer MH.
“Tissue-specific DNA methylation loss during ageing and carcinogenesis is linked to chromosome structure, replication timing and cell division rates.”
Nucleic Acids Res, 46(14):7022-7039, 2018.

Yang JS, Garriga-Canut M, Link N, Carolis C, Broadbent K, Beltran-Sastre V, Serrano L and Maurer SP.
“rec-YnH enables simultaneous many-by-many detection of direct protein-protein and protein-RNA interactions.”
Nat Commun, 9(1): 3747, 2018.

Zapata L, Pich O, Serrano L, Kondrashov FA, Ossowski S and Schaefer MH.
“Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome.”
Genome Biol, 19(1): 67, 2018.