Integrative Biomedicine

The Integrative Biomedicine Laboratory has a curiosity-driven, fundamental research program on animal neurophysiology using Drosophila as a model system and a goal-oriented, translational program focusing on disease modelling and cell targeting techniques for human cells. 

In our curiosity-driven program, we rely heavily on genetic approaches, such as neurogenetics, targeted genome editing, and intersectional genetics to study pathways involved in interorgan communication events – typically between the central nervous system and peripheral organs.

In our translational program, we model human neurodegenerative disease and develop new tools for human cell type-specific treatments. Briefly, we use synthetic and computational biology to engineer new genetic tools for human cell type diagnosis and treatment. We are building genetic systems based on intersectional genetics concepts (developed and tested in Drosophila) and plan to test these systems directly on human organoids derived from our custom-engineered human induced pluripotent stem cell reporter lines.

Two other projects are also underway studying:

  1. the causative-role of repetitive-element activity (focusing on LINE1 retrotransposable elements) in age-dependent neurodegeneration using heterologous in vitro and in vivo models
  2. molecular mechanisms of peripheral neuropathies, where we study a gene, ARGHEF10, which has been implicated in peripheral neuropathies and Charcot-Marie-Tooth disease by using both Drosophila and engineered human induced pluripotent stem cell models.
Graphical Abstract
  • 2021-23 - "Neuronal regulators of relaxin signalling pathway" EXPL/BIA-BID/1524/2021, FCT National Grant, Amount €50 000; PI: A Garelli. Co-PI: R Zanini.
  • 2021-23 -  "Neurogenetics of confinement-induced behavioral alterations" EXPL/BIA-COM/1296/2021, FCT National Grant, Amount €50 000; PI: F Heredia. Co-PI: A Macedo.
  • 2018-22 -"Neuroendocrine control of tissue remodelling" PTDC/BIA-BID/31071/2017, FCT National Grant, Amount €239 949; PI: A Garelli. Co-PI: A Gontijo.
  • 2018-22 - "Retrotransposition and aging-associated neuronal function decline" PTDC/MED-NEU/30753/2017, FCT National Grant, Amount €239 948; PI: F Heredia. Co-PI: A Gontijo.
  • 2018-19 - “Engineering biosensors for human cell type and state diagnosis using synthetic digital computation”. MIT EXPL/BIO/0097/2017, MIT Portugal FCT. Amount €87 458; PI: A. Gontijo Co-PIs: C Brito/T Lu.
  • 2017-19 - “Molecular physiology and evolution of a new developmental stability pathway”. 2016/09659-3, FAPESP, Brazil. Amount ~$45 000; PI: T. Torres. Co-PI: A Gontijo/A Garelli.
  • 2016-18 - “Interorgan communication during growth perturbation”. PTDC/BEXBCM/1370/2014 FCT, Portugal. Amount €199 950 (to A Gontijo); PI: A Gontijo.
  • 2015-17 -  “Generation of genetically-modified hiPSC cell lines for the development of a new transcriptional program sensor system for diagnoses and therapeutics”. iNOVA4Health Seed Projects, FCT, Portugal: Amount €20 000 (to A Gontijo); PI: A Gontijo. Co-PIs: C Brito/J Ramalho.
  • 2013-17 - “ “Marie Sklodowska Curie” Career Integration Grant (FP7-PEOPLE-2013-CIG) “FLY-PHY” Amount: €100 000 PI: Alisson Gontijo.
  • 2013-18 2012FCT Investigator Programme “Development Grant”. Covers PI Salary. Amount: ~€252.000 PI: Alisson Gontijo.
  • 2008-10 -  “FLYMETASTASIS”, FP7-PEOPLE-2007-IEF; Amount: €159 166; PIs: A Gontijo/M Dominguez.

Heredia F, Volonté Y, Pereirinha J, Fernandez-Acosta M, Casimiro AP, Belém CG, Viegas F, Tanaka K, Menezes J, Arana M, Cardoso GA, Macedo A, Kotowicz M, Prado Spalm FH, Dibo MJ, Monfardini RD, Torres TT, Mendes CS, Garelli A, Gontijo AM. The steroid-hormone ecdysone coordinates parallel pupariation neuromotor and morphogenetic subprograms via epidermis-to-neuron Dilp8-Lgr3 signal induction. Nat Commun. 2021 Jun 7;12(1):3328. doi: 10.1038/s41467-021-23218-5.

Imambocus BN, Wittich A, Tenedini F, Zhou F, Hu C, Sauter K, Varela EM, Herédia F, Casimiro AP, Macedo A, Schlegel P, Yang R, Miguel-Aliaga I, Pankratz M,Gontijo AM, Cardona A, Soba P. Discrete escape responses are generated by neuropeptide-mediated circuit logic. bioRxiv 2020.09.22.307033; doi: https://doi.org/10.1101/2020.09.22.307033

Macedo A, Gontijo AM. The intersectional genetics landscape for humans. Gigascience. 2020 Aug 1;9(8):giaa083. doi: 10.1093/gigascience/giaa083.

Gontijo AM, Garelli A. The biology and evolution of the Dilp8-Lgr3 pathway: A relaxin-like pathway coupling tissue growth and developmental timing control. Mech Dev. 2018 Apr 30. pii: S0925-4773(18)30072-8. doi: 10.1016/j.mod.2018.04.005.

Garelli A, Heredia F, Casimiro AP, Macedo A, Nunes C, Garcez M, Dias AR, Volonte YA, Uhlmann T, Caparros E, Koyama T, Gontijo AM. Dilp8 requires the neuronal relaxin receptor Lgr3 to couple growth to developmental timing. Nat Commun. 2015 Oct 29. 6:8732. doi: 10.1038/ncomms9732.

de Castro Marcondes JP, de Oliveira ML, Gontijo AM, de Camargo JL, Salvadori DM. Genetic instability persists in non-neoplastic urothelial cells from patients with a history of urothelial cell carcinoma. PLoS One. 2014 Jan 22;9(1):e86162. PMID: 24465937

Garelli A, Gontijo AM, Miguela V, Caparros E, Dominguez M. Imaginal discs secrete insulin-like peptide 8 to mediate plasticity of growth and maturation. Science. 2012 May 4;336(6081):579-82. doi: 10.1126/science.1216735.

Gontijo AM, Miguela V, Whiting MF, Woodruff RC, Dominguez M. Intron retention in the Drosophila melanogaster Rieske Iron Sulphur Protein gene generated a new protein. Nat Commun. 2011;2:323. doi: 10.1038/ncomms1328.

Gontijo AM, Aubert S, Roelens I, Lakowski B. Mutations in genes involved in nonsense mediated decay ameliorate the phenotype of sel-12 mutants with amber stop mutations in Caenorhabditis elegans. BMC Genet. 2009 Mar 20;10:14. doi: 10.1186/1471-2156-10-14.

Lopez-Rubio JJ, Gontijo AM, Nunes MC, Issar N, Hernandez Rivas R, Scherf A. 5′ flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites. Mol Microbiol. 2007 Dec;66(6):1296-305. doi: 10.1111/j.1365-2958.2007.06009.x.

Pinhal D, Gontijo AM, Reyes VA, Salvadori DM. Viable human buccal mucosa cells do not yield typical nucleoids: impacts on the single-cell gel electrophoresis/Comet assay. Environ Mol Mutagen. 2006 Mar;47(2):117-26. doi: 10.1002/em.20174.

Freitas-Junior LH, Hernandez-Rivas R, Ralph SA, Montiel-Condado D, Ruvalcaba-Salazar OK, Rojas-Meza AP, Mâncio-Silva L, Leal-Silvestre RJ, Gontijo AM, Shorte S, Scherf A. Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites. Cell. 2005 Apr 8;121(1):25-36. doi: 10.1016/j.cell.2005.01.037.

Gontijo AM, Green CM, Almouzni G. Repairing DNA damage in chromatin. Biochimie. 2003 Nov;85(11):1133-47. doi: 10.1016/j.biochi.2003.10.018.

Azevedo L, Gomes JC, Stringheta PC, Gontijo AM, Padovani CR, Ribeiro LR, Salvadori DM. Black bean (Phaseolus vulgaris L.) as a protective agent against DNA damage in mice. Food Chem Toxicol. 2003 Dec;41(12):1671-6. doi: 10.1016/s0278-6915(03)00173-x

de Miranda Cabral Gontijo AM, Barreto RE, Speit G, Valenzuela Reyes VA, Volpato GL, Favero Salvadori DM. Anesthesia of fish with benzocaine does not interfere with comet assay results. Mutat Res. 2003 Jan 10;534(1-2):165-72. doi: 10.1016/s1383-5718(02)00276-0.
 
 
 

  • 2021 - EMBO Short Term Fellowship Award to Duarte Brandão (to visit H Acloque's lab, Paris, France)
  • 2020 -EMBO Short Term Fellowship Award to Ednilson Varela (to visit P Soba's lab, Hamburg, Germany)
  • 2018-19 - Portuguese League Against Cancer (LPCC) Fellowship Award to André Macedo.
  • 2013-19 - FCT Postdoctoral Fellowship Award to Dr Fabiana Heredia.
  • 2013-16 - FCT PhD Fellowship Award to Angela Dias.
  • 2013-18 - Investigator Grant (Associate Professor level) to Dr. Alisson Gontijo, FCT (Portuguese Research Council), Portugal.
  • 2013 - Gulbenkian Training Program in Bioinformatics (GTPB) Champion to Alisson Gontijo, Portugal.
Gontijo lab participates in characterization of neuronal circuit in larvae in response to dangerous stimuli

Animals have specific ways of escaping external danger. And a collaborative study now reveals that there are signals promoted by molecules released by neurons to make fruit fly larvae (Drosophila melanogaster) escape harmful external stimuli.

Current national collaborations

  • Dr. Claudia Almeida CEDOC, Portugal
  • Dr. José Ramalho CEDOC, Portugal
  • Dr. Luis Teixeira IGC, Portugal
  • Dr. Carlos Ribeiro FC, CCU, Portugal

Current International collaborations

  • Dr. Javier Bravo-Cordero Mount Sinai, EUA
  • Dr. Musa Mhlanga/J Scholefield Radboud U., Países Baixos & CSIR, Africa do Sul
  • Prof. Dr. Tatiana Torres USP, Brasil
  • Prof. Dr. Christian Wegener U. Würzburg, Alemanha
  • Dr. Peter Soba U. Bonn, Alemamha

Principal Investigator

Alisson M. Gontijo

Team

Fabiana Heredia
Associate Researcher/PhD
Andrés Garelli
Associate Researcher/PhD
Juliane Menezes
Associate Researcher, PhD
Magdalena Fernandez
Post-Doctoral Fellow/PhD
Rebeca Zanini
Post-Doctoral Fellow/PhD
Angela Dias
PhD Student/MSc
Duarte P. Brandão
PhD Student/MSc
Ednilson Varela
PhD Student/BSc
Carolina Pinto
MSc Student/BSc
João Nabo
MSc Student/BSc
Mafalda Gualdino
MSc Student/BSc
Rafaela Pina
MSc Student
Valentine Louis
Trainee/BSc