Theoretical and Computational Biosciences

Theoretical and Computational Biochemistry
TCB Research Labs

The TCB Group develops research in computational sciences applied to human health. The group uses in silico approaches to decode multi-omics profiles and simulate biomolecular interactions, with the final goal of discovering new biomarkers and drugs.


The TCB group aims to improve our knowledge about the molecular mechanisms underlying gene expression regulation. Hence, we are combining genome-wide profiles of genome, epigenome, and transcriptome to unveil how molecular alterations can disrupt cell homeostasis. In such line, we have contributed for the development of computational pipelines to identify transcription noise and to process high-throughput sequencing profiles of nascent transcripts. Moreover, we are exploring the crosstalk between cancer cells and respective microenvironment to identify future prognostic biomarkers or therapeutic targets. This work has been developed within multidisciplinary networks, including hospitals, to foster precision medicine approaches into the biomedical research and healthcare.


In parallel, through biomolecular simulations we aim to understand how enzymes catalyze their reactions and to use this knowledge to rationally develop new, more effective, and “greener” biocatalysts for the pharmaceutical, chemical and food industries. We are also involved in the development of computational drug development methodologies and have established strategic collaboration networks with several experimental research groups, bridging fundamental and applied research. In particular, we have designed target-specific protocols for the identification of promising drug candidates for experimental testing and have been involved in the rationalization of experimental results, and in drug optimization. In addition, we currently maintain open scientific databases of reference on Biofilm research ( and on Legionella outbreaks (

Recent publications
Silvia Carvalho; Luna Zea-Redondo; Tsz Ching Chloe Tang; Philipp Stachel-Braum; Duncan Miller; Paulo Caldas; Alexander Kukalev; Sebastian Diecke; Stefanie Grosswendt; Ana Rita Grosso; Ana Pombo. 2024. SRRM2 splicing factor modulates cell fate in early development. Biology Open, DOI: 10.1242/bio.060415
Paulo Caldas; Mariana Luz; Simone Baseggio; Rita Andrade; Daniel Sobral; Ana Rita Grosso. 2024. Transcription readthrough is prevalent in healthy human tissues and associated with inherent genomic features. Communications Biology, DOI: 10.1038/s42003-024-05779-5
Bruno ACardoso; Mafalda Duque; Ana Gírio; Rita Fragoso; Mariana LOliveira; James RAllen; Leila RMartins; Nádia CCorreia; André Bortolini Silveira; Alexandra Veloso; Shunsuke Kimura; Lisa Demoen; Filip Matthijssens; Sima Jeha; Cheng Cheng; Ching-Hon Pui; Ana RGrosso; João LNeto; Sérgio FDe Almeida; Pieter Van Vlieberghe; Charles GMullighan; JAndres Yunes; David MLangenau; Françoise Pflumio; João TBarata. 2023. CASZ1 upregulates PI3K-AKT-mTOR signaling and promotes T-cell acute lymphoblastic leukemia. Haematologica, DOI: 10.3324/haematol.2023.282854
Sabino, JC; de Almeida, MR; Abreu, PL; Ferreira, AM; Caldas, P; Domingues, MM; Santos, NC; Azzalin, CM; Grosso, AR; de Almeida, SF. 2022. Epigenetic reprogramming by TET enzymes impacts co-transcriptional R-loops. eLife, 11, DOI: 10.7554/eLife.69476
Sobral, D; Francisco, R; Duro, L; Videira, PA; Grosso, AR. 2022. Concerted Regulation of Glycosylation Factors Sustains Tissue Identity and Function. BIOMEDICINES, 10, DOI: 10.3390/biomedicines10081805