Dr. Carmela Gissi, Dr. David Horner, Dr. Giulio Pavesi

The main research interests of the group are focused on bioinformatics, comparative genomics and molecular evolution. Particular interest is paid to the development of algorithms and computational tools for genomic analyses, most of which are freely accessible on the Internet and widely used by researchers worldwide, and to studies on the mitochondrial genomes of chordates, both at the evolutionary dynamics and phylogenetic levels. The group was founded by Prof. Graziano Pesole, now at the University of Bari, with whom we still collaborate on a regular basis. In addition to our own research projects, the group cooperates with other research teams in the department and in other institutions to provide an in silico counterpart to in vitro and in vivo analyses and/or to perform bioinformatics and phylogenetic analyses of genes of particular interest.

See www.beacon.unimi.it for further information.

Research topics:

1. Comparative mitogenomics in Ascidiacea and other metazoans

Gissi, Griggio, Lupi

The aim of this research is to unravel the evolutionary peculiarities and the structural-functional relationships of the mitochondrial genome (mtDNA) of metazoans, with particular interest towards the group of ascidians (Chordata, Tunicata). Thus, the metazoan mtDNA is analysed both as a model system to understand the evolutionary mechanisms of a genome as a whole, and as phylogenetic marker. In order to clarify the evolutionary dynamics of ascidian mtDNAs, we have sequenced the complete mtDNA of ascidians belonging to distinct taxonomic orders, including the model ascidian Ciona intestinalis. The comparative mitogenomics analyses have revealed the existence of cryptic species in C. intestinalis and of a extreme variability within ascidians in gene order, gene content, compositional features and genome size, being these features really extraordinary in ascidians compared to other deuterostomes. The study of the gene order rearrangement mechanisms in ascidians and other metazoans is currently in progress. As initial effort in the study of the nucleus-mitochondrion co-evolution in Metazoa, we are currently developing comparative bioinformatics methods aimed at the identification of the regulatory signals involved in the mtDNA replication/transcription and at the investigation of their evolution. The group of Dr. Tiziana Castrignanò at CASPUR (Roma) cooperates on this last topic. 

2. Molecular phylogenetic and evolutionary analyses

Horner, Gissi, Pavesi, Chiara, Lupi.

The BEACON group possesses considerable expertise in the formulation and execution of molecular phylogenetic analyses of both nucleotide and protein sequences. Our interests include the molecular evolution of nuclear and mitochondrial genes of chordates as well as the evolution of genes which are specific to protists that possess hydrogenosomes or mitosomes - specialized mitochondria that have lost the capacity to mediate oxidative respiration but which perform other critical functions for the organisms which host them. Among others, the BEACON group worked on the molecular phylogeny of amphibians, and on the position of Rodentia and Glires (Rodentia plus Lagomorpha) in the mammalian phylogenetic tree. Recent analyses have also been conducted at the gene structural level, that is, by comparing the exon-intron structure of homologous genes at different levels of divergence, for the identification and characterization of intron gain or loss events and/or the assessment of the degree of conservation of alternative splicing events.

3. Analysis of Next-Generation Sequencing Data

Horner, Pavesi, Gissi, Chiara, Piccolo, Zambelli 

The advent of several new ultra-high-throughput nucleic acid sequencing methodologies (NGS), notably the Roche 454, Illumina Solexa and ABI SOLiD platforms allows the generation of millions of short sequence reads. These new types of sequencing data can be used to address numerous different biological problems including, but not restricted to: genome resequencing and the characterization of SNPs and genome rearrangements, characterization of entire transcriptomes, identification of populations of small RNAs, of physiological binding sites of transcription factors, of histone modifications and epigenetic modifications. However, the nature of the data (millions of reads of limited length) requires the development of novel bioinformatics approaches for each of the proposed applications. Our group is at the forefront of this exciting new research area, developing tools and facilities for microRNA discovery, transcription factor binding site analysis, mRNA splicing, mitochondrial transcriptome analyses, nuclear transcript and protein-mRNA interaction characterization. 

4. Tools and algorithms for the functional annotation of genomic data

Horner, Pavesi, Piccolo, Zambelli 

This work, aimed at the development of tools and applications for the large-scale analysis of genomic data, has resulted in the implementation and distribution of several different software tools, such as: 1) CSTminer and GenoMiner, for the identification and characterization of Conserved Sequence Tags corresponding to unannotated genes or regulatory elements through full-length genome comparisons; 2) WebVar, which permits the study of site-specific variability in genomic or protein sequences; 3) ASPIC, for genomic-EST alignments, aimed at the detection and prediction of alternative splicing events and transcripts; 4) GeneSyn, for the comparative study of synteny across multiple genomes; 5) Exalign, for the comparison of the exon-intron structure of homologous genes. The group of Dr. Flavio Mignone at the Faculty of Pharmacy cooperates on these topics.

5. Tools and algorithms for the analysis of regulatory regions in eukaryotic genomes

Pavesi, Zambelli

This line is aimed at designing in silico techniques for the identification and characterization of elements regulating gene expression at transcriptional and post-transcriptional levels In particular, we developed or are currently developing methods for 1) the discovery of conserved transcription factor binding sites in sequences from either co-regulated or homologous genes (or both), or derived from NGS experiments; 2) the description of the binding specificity of a given transcription factor given a set of validated sites, so to be able to predict with accuracy additional sites 3) the integration of expression and sequence data with the final goal of predicting the expression pattern of a gene from the sequence of its regulatory regions 4) the discovery of conserved sequence and structure motifs in non-coding RNAs, with particular interest in signals in mRNA UTRs, often responsible for translation efficiency and transcript fate modulation.

Publications

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