Generation of the Phylogenetic Tree of Tubulin and Its Binding Sites for Drug Interactions
Reference persons JACEK ADAM TUSZYNSKI
External reference persons Prof. Richard Luduena, University of Texas Health Sciences Center, San Antonio, USA
Research Groups 28- biomedica
Thesis type COMPUTATIONAL
Description This projectís purpose is to show differences and similarities between human tubulin and those of the other species for which sequences can be found, in order to understand the evolutionary processes of this important protein. Tubulin is a globular protein forming a stable dimer alpha/beta. Tubulin polymerizes into microtubules, which are the major components of the eukaryotic cytoskeleton. Microtubules play an important role in many essential cellular processes, including mitosis. Tubulin-binding drugs kill cancerous cells by inhibiting microtubule dynamics, which are required for DNA segregation and therefore cell division. In eukaryotes there are six members of the tubulin superfamily, although not all of them are present in all species. Tubulin was long thought to be specific to eukaryotes. More recently, however, several prokaryotic proteins have been shown to be related to tubulin. Tubulin is part of a superfamily, made up by six other families: alpha-, beta-, gamma-, delta-, epsilon and zeta-tubulins. All drugs that are known to bind to human tubulin bind to β-tubulin. These include paclitaxel, colchicine, and the vinca alkaloids, each of which have a distinct binding site on β-tubulin. Human β-tubulins subtypes include:
TUBB TUBB1 TUBB2A TUBB2B TUBB2C TUBB3 TUBB4 TUBB4Q TUBB6. This project consists in the following main tasks:
1. Find all tubulin sequences in the publicly available databases (e.g. Uniprot)
2. Perform multiple alignments between human tubulin sequences and those of other species;
3. Find conserved and variable regions in the sequences, especially in the known binding sites for tubulin binding sites.
4. Create phylogenetic trees of tubulin isotypes (alpha, beta, gamma, etc.)
The phylogenetic trees can be generated by web server Phylogeny.fr , which runs and connects various bioinformatics programs to reconstruct a robust phylogenetic tree from a set of sequences. ClustalX2.1 can be used to perform multiple sequence alignments, PhyML to construct the phylogenetic trees. All the phylogenetic trees can be visualized using iTOL.
Required skills introductory bioinformatics, ability to search and extract information from databasis, rudimentary knowledge of sequence alignment algorithms
Deadline 02/03/2024 PROPONI LA TUA CANDIDATURA