Dissertation defence (Physiology): MSc Opeyemi Olotu


15.12.2023 at 12.00 - 16.00
MSc Opeyemi Olotu defends the dissertation in Physiology titled “Function of germline-specific ribonucleoprotein granules - from germline to cancer” at the University of Turku on 15 December 2023 at 12.00 (University of Turku, Medisiina D, Alhopuro lecture hall, Turku).

Opponent: Associate Professor Geert Hamer (University of Amsterdam, the Netherlands)
Custos: Professor Noora Kotaja (University of Turku)

Doctoral Dissertation at UTUPub: https://urn.fi/URN:ISBN:978-951-29-9549-3

The audience can participate in the defence by remote access: https://utu.zoom.us/j/68632375632


Summary of the Doctoral Dissertation:

Cells (germ cells) that eventually develop into mature sperm usually go through several stages, which is accompanied by complex genome expression. If this complexity is not controlled, it leads to impaired germ cell development and thus to male infertility. In order to overcome the burden, the germ cells contain some granule-like structures (known as germ granules) in their environment that serve as the centre for proper control of their genome expression.

In my doctoral thesis, I clarified the functions of two types of germ granules, the intermitochondrial cement (IMC) and the chromatoid body (CB), and their contribution to male fertility. I investigated the protein composition of the IMC and demonstrated its central role in the production of PIWI-interacting RNAs (piRNAs). We also identified two novel IMC components, EXD1 and EXD2, and characterized their association with germ granules and their interaction with other important factors required for male fertility.

Furthermore, I was able to show that germ granule-like structures also occur in the cytoplasm of cancer cells. A germ cell specific protein (DDX4) found in these granules, appear in many types of tumors. Deletion of DDX4 in cancer cells led to an imbalance of the transcriptome and a disrupted splicing landscape of genes that contribute to cancer growth and invasiveness, and consequently retarded tumor growth. Moreover, the presence of DDX4 granules in human cancer samples was shown to correlate with a poor prognosis for the patient. This implies that cancer cells also utilize these germ cell-specific properties in germ granules to enhance cancer formation, progression and metastasis.

The results of this study highlight the importance of germ granules in the piRNA pathway during sperm formation and provide evidence for the novel role of germ granule components in transcriptome control in cancer cells that promote malignant properties.

Overall, this PhD study elucidates the understanding of molecular mechanisms of germ granule-mediated RNA regulation in male fertility. Also, the knowledge from germ cell to cancer research provides new insights into the development of tools for cancer classification and prognosis.
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