[Jul. 14] D5 Seminar-Dr. Anne Goriely (University of Oxford)

June 19 2025

The "D5 Medical & Life Science Seminar" course will be offered by International Research Center for Medical Sciences (IRCMS). It will run from May 2025 to March 2026, with lectures given by scientists who are affiliated with IRCMS or in collaboration with researchers at IRCMS. The lectures will be given once a month, in English, and by leading scientists in the relevant research field. Students will be taught: 1) how normal physiological functions are maintained in the human body; 2) how these systems become abnormal under certain pathophysiologic conditions; 3) why stem cells are important in animal development and homeostasis; 4) how stem cell-based approaches can help us understand disease mechanisms and find potential cure for diseases related to stem cell malfunction (e.g., cancer, aging).

Anyone who wants to join is welcome.
For students who have registered for the course, please check your attendance in Moodle.

Date      : July 14, 2025 (Monday)
               

Format  : Online

Time      : 16:00 - 17:00 (JST)
               

Speaker : Dr. Anne Goriely (University of Oxford)
               

Title       : The fine balance between genome maintenance and selfishness in human testes

Abstract  :

It is now well-established that our genomes mutate at a slow but constant rate of 30-100 new point mutations per generation. Although most de novo mutations (>80%) originate from the father and increase in frequency at the rate 1-2 mutation/paternal year, very little is known about the cellular mechanisms that allow the adult testis to reconcile the contradictory demands for abundant sperm production - that takes place over many decades - and the need to maintain genome integrity (i.e. low mutation rate) across generations.

In this presentation I will discuss how the study of de novo mutations associated with rare human disorders provides an entry point to discover fundamental mechanisms operating in the testes and the importance of the regulation of spermatogenesis for human disease, genome diversity and evolution.

2-3 Major Papers

1. Wood KA^, Tong RS^, Motta M^, Cordeddu V, Scimone ER, Bush SJ, Maxwell D, Giannoulatou E, Caputo V, Traversa A, Mancini C, Ferrero GB, Benedicenti F, Grammatico P, Melis D, Steindl K, Brunetti-Pierri N, Trevisson E, Wilkie AOM, Lin AE, Cormier-Daire V, Twigg SRF, Tartaglia M*, Goriely A*, 2024: SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline; Am J Hum Genet 111:1-17 [PMC11444041]

2. Maher GJ, Ralph HK, Ding Z, Koelling N, Mlcochova H, Giannoulatou E, Dhami P, Paul DS, Stricker SH, Beck S, McVean G, Wilkie AOM & Goriely A*, 2018: Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes. Genome Res. 28(12):1779-1790. (*corresponding author) [PMC6280762]

3. Goriely A, McVean GAT, Rojmyr M, Ingemarsson B & Wilkie AOM, 2003: Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line. Science 301: 643-646. [PMID: 12893942]

Supported by AMED-ASPIRE (International and Interdisciplinary Research on Germ Cell Dynamics and Transgenerational Health Risks)

Flyer: (Click to enlarge)