Subarea 5: Computational and Systems Biology of Aging

Subarea 5 focuses on the development of methods to analyse and understand complex biological systems. This work includes the design of computer algorithms and biostatistical approaches as well as the development of novel Omic strategies (i.e. genomics/epigenomics, transcriptomics, proteomics, and metabolomics) to study aging and aging-related diseases. According to the FLI, due to the Subarea's expertise in computational data analysis, it is deeply interconnected with all other Subareas. The Subarea hosts two critical core facilities (Life Science Computing, Proteomics) and provides consulting services in statistics. Furthermore, it organizes courses on data analysis and statistics.

The research is defined by five focus areas:

  • Mapping extrinsic and intrinsic factors influencing stem cells during aging,
  • Integration of spatiotemporal proteomics and transcriptomics data,
  • Comprehensive evaluation of qualitative and quantitative expression changes,
  • Identification and analysis of epigenomic alterations during aging and age-related diseases, and
  • Network analysis of genomic, transcriptomic and epigenomic alterations during aging.

Research focus of Subarea 5.

The biology of aging can be viewed as a multilayered array of networks at the level of organs, cells, molecules, and genes. The FLI wants to meet this complexity by establishing the new Subarea on “Computational and Systems Biology of Aging”. The overall goal is to interconnect research at different scales, taking place in Subareas 1-4 of the Institute’s research program. The new group on Systems Biology will integrate data from networks at multiple scales and will thus point to mechanisms and interactions that would not be seen in unilayer approaches.

Publications

(since 2016)

2024

  • Aging-associated decline of phosphatidylcholine synthesis is a malleable trigger of natural mitochondrial aging
    Poliezhaieva T, Alonso Pernas P, Espada L, Bayar M, Li Y, Melike Dönertaş H, A.Ermolaeva M
    bioRxiv 2024, https://doi.org/10.1101/2024.04.
  • Remodelling of the cardiac extracellular matrix proteome during chronological and pathological ageing.
    Santinha D, Vilaça A, Estronca L, Schüler SC, Bartoli C, De Sandre-Giovannoli A, Figueiredo A, Quaas M, Pompe T, Ori** A, Ferreira** L
    Mol Cell Proteomics 2024, 23(1), 100706 ** co-corresponding authors
  • Mis-spliced transcripts generate de novo proteins in TDP-43-related ALS/FTD.
    Seddighi S, Qi YA, Brown AL, Wilkins OG, Bereda C, Belair C, Zhang YJ, Prudencio M, Keuss MJ, Khandeshi A, Pickles S, Kargbo-Hill SE, Hawrot J, Ramos DM, Yuan H, Roberts J, Sacramento EK, Shah SI, Nalls MA, Colón-Mercado JM, Reyes JF, Ryan VH, Nelson MP, Cook CN, Li Z, Screven L, Kwan JY, Mehta PR, Zanovello M, Hallegger M, Shantaraman A, Ping L, Koike Y, Oskarsson B, Staff NP, Duong DM, Ahmed A, Secrier M, Ule J, Jacobson S, Reich DS, Rohrer JD, Malaspina A, Dickson DW, Glass JD, Ori A, Seyfried NT, Maragkakis M, Petrucelli L, Fratta P, Ward ME
    Sci Transl Med 2024 (epub ahead of print)
  • Reducing the metabolic burden of rRNA synthesis promotes healthy longevity in Caenorhabditis elegans.
    Sharifi* S, Chaudhari* P, Martirosyan A, Eberhardt AO, Witt F, Gollowitzer A, Lange L, Woitzat Y, Okoli EM, Li H, Rahnis N, Kirkpatrick J, Werz O, Ori A, Koeberle A, Bierhoff** H, Ermolaeva** M
    Nat Commun 2024, 15(1), 1702 * equal contribution, ** co-corresponding authors
  • Leiomodin 1 promotes myogenic differentiation by modulating Sirtuin 1
    Späth* E, C.Schüler* S, Heinze I, Dau T, Minetti A, Hofmann M, von Maltzahn** J, Ori** A
    bioRxiv 2024, https://doi.org/10.1101/2024.03. * equal contribution, ** co-corresponding authors
  • Transthyretin orchestrates vitamin B12-induced stress resilience
    Stein G, S Aly J, Manzolillo A, Lange L, Riege K, Hussain I, A Heller E, Cubillos S, A Ernst T, A Huebner C, Turecki G, Hoffmann S, Engmann O
    bioRxiv 2024, 10.1101/2024.02.07.578164
  • Npbwr1 signaling mediates fast antidepressant action
    Stein G, S.Aly J, Lange L, Manzolillo A, Riege K, Brancato A, A.Hübner C, Turecki G, Hoffmann S, Engmann O
    bioRxiv 2024, 10.1101/2024.02.02.578166
  • An artificial intelligence-assisted clinical framework to facilitate diagnostics and translational discovery in hematologic neoplasia.
    Tang M, Antić Ž, Fardzadeh P, Pietzsch S, Schröder C, Eberhardt A, van Bömmel A, Escherich G, Hofmann W, Horstmann MA, Illig T, McCrary JM, Lentes J, Metzler M, Nejdl W, Schlegelberger B, Schrappe M, Zimmermann M, Miarka-Walczyk K, Patsorczak A, Cario G, Renard BY, Stanulla M, Bergmann AK
    EBioMedicine 2024 (epub ahead of print)
  • SEPTIN10-mediated crosstalk between cytoskeletal networks controls mechanotransduction and oncogenic YAP/TAZ signaling.
    Weiler SME, Bissinger M, Rose F, von Bubnoff F, Lutz T, Ori A, Schirmacher P, Breuhahn K
    Cancer Lett 2024 (epub ahead of print)

2023

  • Author Correction: Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer.
    Akdemir KC, Le VT, Chandran S, Li Y, Verhaak RG, Beroukhim R, Campbell PJ, Chin L, Dixon JR, Futreal PA, PCAWG Structural Variation Working Group, PCAWG Consortium
    Nat Genet 2023, 55(6), 1079