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Louis-Jeantet prize lectures

Monday, 12 September 09:45 - 10:45
Room: Musensaal (Saal 2.0)

Introduction by Sir Paul Nurse, UK - Chairman of the Scientific Committee of the Louis-Jeantet Foundation

Andrea Ballabio IT

Telethon Institute of Genetics and Medicine (TIGEM), Napoli

The awesome lysosome
In the early 50s, Christian De Duve identified a new cellular structure, the lysosome, defined as the cell’s “suicide bag” (de Duve, 2005). Sixty years later, it is clear that the lysosome greatly exceeded the expectations of its discoverer. Over 50 different types of lysosomal storage diseases have been identified, each due to the deficiency or malfunction of a specific lysosomal protein. In addition, an important role of the lysosome has been unveiled in several common human diseases, such as cancer, obesity, neurodegenerative diseases, and infection. Recent studies have led to the identification of a lysosome-to-nucleus signaling pathway and a lysosomal gene network that regulate cellular clearance and energy metabolism. These observations have opened a completely new field of research and changed our traditional view of the lysosome from a dead-end organelle to a control center of cell metabolism. An important challenge for the future will be to exploit these discoveries to identify modulators of lysosomal function that may be used to treat human diseases.

Biography

Born in 1957 in Naples, Italy, Andrea Ballabio studied Medicine at the Federico II University in Naples and took residency in Pediatrics at the same university. He was a post-doctoral fellow at Guy’s Hospital in London, UK, and then at the International Institute of Genetics and Biophysics in Naples, Italy. He spent many years in the US where he became Associate Professor at the Department of Molecular and Human Genetics, Baylor College of Medicine, and Co-Director of the Baylor Human Genome Center, in Houston, Texas. In 1994 he moved back to Italy to become director and founder of the Telethon Institute of Genetics and Medicine (TIGEM), a flagship institute for the study of rare genetic diseases, which is managed by the Italian Telethon Foundation. He is currently also Professor of Medical Genetics at the Federico II University in Naples and Visiting Professor at both Baylor College of Medicine, and at the University of Oxford, UK. He has received many awards and recognitions for his work. He was President of the European Society of Human Genetics, EMBO Council member. In 2007, the President of the Italian Republic appointed him Knight of the Order of Merit. He received the European Society of Human Genetics International Award (2007) and the Advanced Investigator Award of the European Research Council (2010). In 2006, he was Torchbearer at the XX Torino Olympic Winter Games.

John Diffley UK

The Francis Crick Institute, London

Reconstituting Chromosome Replication
The eukaryotic cell cycle coordinates the accurate duplication and segregation of the genome during proliferation.  The large genomes of eukaryotic cells are replicated from multiple replication origins during S phase.  These origins are not activated synchronously at the beginning of S phase, but instead fire throughout S phase according to a pre-determined, cell type specific program.Ensuring that each origin is efficiently activated once and only once during each S phase is crucial for maintaining the integrity of the genome.  This is achieved by a two-step mechanism.  The first step, known as licensing, involves the loading of the Mcm2-7 proteins into pre-replicative complexes (pre-RCs) at origins. In the second step, the MCM helicase is activated by a large set of ‘firing factors’. These two steps are differentially regulated by cyclin dependent kinase (CDK): licensing is inhibited by CDK, whilst firing requires CDK. As a consequence, licensing can only happen during G1 phase, when CDK activity is low, and origin firing cannot occur during G1 phase.We have recently described the reconstitution of the initiation of eukaryotic DNA replication with purified proteins.  I will describe recent results on the reconstitution the entire replisome, and will describe how chromatinised templates are replicated in vitro.

Biography

John Diffley was born 1958 in New York (USA) and studied in his home town (New York University) where he received his BA and PhD. Following a period as a post-doctoral fellow at Cold Spring Harbor Laboratory in New-York, he left for the UK in 1990. He continued his research at the Clare Hall Laboratories, where he became the director in 2006. In the same year he was made Deputy Director of the London Research Institute, and in 2015 became Associate Research Director at the Francis Crick Institute. He was elected as a member of EMBO in 1998. He is also a Fellow of the Royal Society, of the American Association for the Advancement of Science, the Academia Europaea, the Academy of Medical Sciences and the European Academy of Cancer Sciences. In 2003 he won the American Paul Marks prize for cancer research.