Ido Proteins Recombinant.

We are the computational Biology and Bioinformatics lab currently located at the Andalusian Center for Developmental Biology [CABD].

Image description By Aida Arcas- 2014

CBBio was founded on 2009 in Barcelona, and moved to Seville in 2013. Our research has resulted in more than 50 peer-reviewed articles, book chapters, invited reviews, and over 50 oral presentations in national and international venues. The group belongs to a Maria de Maeztu Unit [DMC2], an excellence Unit from the SOMM alliance SOMMa.

We are a team of Biologists, Bioinformaticians, and Engineers using computational methods, aiming to understand:

1. how proteins evolve and acquire novel functions
2. how mutations impact a given protein function
3. how is the relationship between molecular evolution and phenotypic evolution.
4. how to better define "protein function"
5. how gene networks evolve in regeneration pathways
6. Our research in TWO selected examples
7. In two examples we illustrate how we apply and combine our research interests to address relevant biological contexts.

A novel MMR pathway:

A gene found in a genetic screening of M. tuberculosis has all the MMR hallmarks. It is a homologue of an archaeal NucS.

By Evolution:

• MMR
• Distribution of NucS.
• NucS is restricted to prokaryotes.
• NucS has a patchy distribution.
• NucS coexists with canonical MMR genes in few species.
• By Structure/function:
• NucS is a two domain protein.
• Individual domains have different taxonomic distributions.
• By Sequence Analyses:
• NucS presents different polymorphisms associated to Multidrug resistance phenotypes.
• The most significant polymorphisms lie within the DNA binding domain.
• Our model: the complete NucS originated as a fusion of two domains in an archeal ancestor. This was transferred at least two times to bacteria. 

Model

Origin and transference of NucS.

Novel mRNA-miRNA interactions relevant to cancer-related pathways .

We analysed the TCGA data to identify potential pairs of mRNA-miRNA that could have predictive value.

mRNA/miRNA pairs specific of lung tumors.

By Transcriptomics:

From 33 TGCA tumor types, only 15 could be used due to partial data.

Inversed correlation patterns alone are not informative.

By Integration:

gene expression of single genes should not be used as proxy for pathway enrichment/depletion status.

In cancer: gene expression should be corrected by methylation and copy number alterations.

Survival analyses should be done with Cox and taken with caution.

Our conclusions: We provide a confident statistical approach to identify novel miRNA-target relationships in different tumour types within cancer-relevant pathways. 

Evolution

Silva.J., et al. 2018 EXD2 governs germ stem cell homeostasis and lifespan by promoting mitoribosome integrity and translation. Nature Cell Biology DOI:10.1038/s41556-017-0016-9 

Castañeda-García, A., et al 2017 A non-canonical mismatch repair pathway in prokaryotes. Nature communications DOI:10.1038/ncomms14246 

Terré B, et al.,2016. GEMC1 is a critical regulator of multiciliated cell differentiation. EMBO Journal.

Andrés-León, E., Cases, I., Arcas, A., & Rojas, A.M. 2016 DDRprot: a database of DNA damage response-related proteins.Arcas, A., et al, 2014. Emergence and evolutionary analysis of the human DDR network: implications in comparative genomics and downstream analyses. Molecular Biology and Evolution. 31:940-61. PMID: 24441036 | doi: 10.1093/molbev/msu046 

Rojas, A.M., et al., 2012. The Ras protein superfamily: Evolutionary tree and role of conserved amino acids. The Journal of Cell Biology. 196:189-201. PMID:22270915 | doi: 10.1083/jcb.201103008. 

Structure/Function

Medina, P. et al., In Prep . Computational analyses of sumoylation in kinases .

Jiménez-Panizo, A., et al. 2019. Non-canonical dimerization of the androgen receptor and other nuclear receptors: implications for human disease. Endocrine Related Cancer. DOI: 10.1530/ERC-19-0132. .

Fuentes-Prior,P., Rojas, A., Hagler, AT., Estébanez-Perpiña,E. 2018 Diversity of Quaternary Structures Regulates Nuclear Receptor Activities. Trends in Biochemical Sciences . DOI:10.1016/j.tibs.2018.09.005 .

Silva.J.,et al 2018 EXD2 governs germ stem cell homeostasis and lifespan by promoting mitoribosome integrity and translation. Nature Cell Biology DOI:10.1038/s41556-017-0016-9 

Castañeda-García, A., et al 2017 A non-canonical mismatch repair pathway in prokaryotes. Nature communications DOI:10.1038/ncomms14246 

Andrés-León, E., Cases, I., Arcas, A., & Rojas, A.M. 2016 DDRprot: a database of DNA damage response-related proteins. DATABASE DOI: 10.1093/database/baw123

Tristán-Clavijo E, et al 2016 Dominant-negative mutation p.Arg324Thr in KCNA1 impairs Kv1.1 channel function in episodic ataxia. Movement disorders. DOI:10.1002/mds.26737 

Terré B, et al 2016. GEMC1 is a critical regulator of multiciliated cell differentiation. EMBO Journal.

Basilico, F.*, et al 2014 The pseudo GTPase CENP-M drives human kinetochore assembly. 

Athiyarath R, et al. 2013. Two Novel Missense Mutations in Iron Transport Protein Transferrin Causing Hypochromic Microcytic Anaemia and Haemosiderosis: molecular characterisation and structural implications. J. Brit Haematol. 163:404-407. PMID:23888904 | doi: 10.1111/bjh.12487 

Pons,T., Paramonov, I., Boullosa, C., Ibañez, K., Rojas, A.M., & Valencia, A. 2013. . A common structural scaffold in CTD phosphatases that supports distinct catalytic mechanisms. Proteins. 82:103-118. PMID:23900790 | doi: 10.1002/prot.24376. 

Rojas, A.M., Fuentes, G., Rausell, A., Valencia, A. 2012. The Ras protein superfamily: Evolutionary tree and role of conserved amino acids. The Journal of Cell Biology. 196:189-201. PMID:22270915 | doi: 10.1083/jcb.201103008. 

Palczewska, M, Casafont I, Ghimire K, Rojas AM, Valencia A, Lafarga M, Mellstrom B, Naranjo JR. 2011. Sumoylation regulates nuclear localization of repressor DREAM. Biochim Biophys Acta 1181:1050-8. PMID: 21070824 | doi: 10.1016/j.bbamcr.2010.11.001. 

Mañes, S, Fuentes, G., Peregil, RM., Rojas AM. and Lacalle, RA. 2010. An isoform-specific PDZ-binding motif targets type I PIP5 kinase beta to the uropod and controls polarization of neutrophil-like HL60 cells. FASEB Journal 24:3381-92. PMID: 20442317 | doi: 10.1096/fj.09-153106. 

Transcriptomics/Tools

Andrés-León, and Ana M Rojas. 2019 . miARma-Seq, a comprehensive pipeline for the simultaneous study and integration of miRNA and mRNA expression data. METHODS . DOI: 10.1016/j.ymeth.2018.09.002 

López-Jiménez E, Rojas AM, Andres-Leon E. 2018. RNA sequencing and Prediction Tools for Circular RNAs Analysis.