Doctoral dissertation

Francesco Tabaro: Proteins involved in prostate cancer characterized via integrated genomic and proteomic data analyses

Tohtori
Sequencing methods provide complementary insights into gene expression regulation in prostate cancer. Identified molecular actors share a common molecular structure organization.

Prostate cancer is a common disease in the Western world. Its molecular features have been studied since the 90s and mechanisms governing its growth were soon identified.

Testosterone is the hormone responsible for male sexual traits differentiation and prostate development. If the molecular systems involved in testosterone sensing in the prostate break, prostate cells may start to divide quickly and generate a tumoral mass. Prostate cancer development is thus sustained by testosterone. Prostate cancer can be controlled with pharmacological treatments but, eventually, it relapses in about a third of patients. At this stage, the tumor can grow with very limited testosterone stimulation and it is defined hormone-refractory prostate cancer.

Using cutting-edge sequencing methods, Francesco Tabaro studied in his doctoral dissertation how the DNA of prostate cancer cells changes its structure during this process and identified a set of genomic features that correlate with progression stages.

In the study genes controlled by these features and the proteins able to bind them were characterized.

"We have confirmed that the testosterone sensing system has a central role in the whole process, and we identify a group of proteins able to cooperate with this core system to sustain progression to more aggressive phenotypes by coordinating the expression of hundreds of genes. We further characterize the molecular structure of these proteins taking advantage of two publicly available databases, DisProt and MobiDB. We find that all these proteins share a common structural organization with extended flexible regions, called intrinsically disordered regions", Tabaro explains.

The phenomenon of intrinsic protein disorder has been studied over the last 30 years but only in recent years has been linked to fundamental cellular processes such as gene expression. In general, proteins use these flexible regions to interact with other molecules and the ones presented in this thesis are no exception.

Identification of these proteins and their structural features may have an impact in drug design by providing novel targets for oncological treatments. Moreover, the results presented in this thesis provide an example of a computational workflow for identification of key proteins in pathological system and their characterization using publicly available data.

The doctoral dissertation of M.Sc. Francesco Tabaro in the field of Computational Biology titled Analysis of Chromatin and Proteins in cancer will be publicly examined in the Faculty of Medicine and Health Technology of  Tampere University at 12 o’clock on Friday 27 November 2020. The Opponent will be Docent Christophe Roos from Helsinki University. Professor Matti Nykter will act as the custos.

The event can be followed via remote connection.

The dissertation is available online at
http://urn.fi/URN:ISBN:978-952-03-1795-9