BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Memento EPFL//
BEGIN:VEVENT
SUMMARY:ChemBio seminar by Prof. Marco Di Antonio (Imperial College London
 \, UK) - CH-635
DTSTART:20231128T161500
DTEND:20231128T171500
DTSTAMP:20260314T202301Z
UID:a4e749286718537505fcdfdd4c543001298b676b0fab0137cf94a0ca
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Marco Di Antonio\, Imperial College London\, UK\nTitle: 
 Long-range G-G base pairing regulates chromatin architecture and promotes 
 RNA condensation in neurodegenerative diseases\n\nAbstract:\nLink to PDF\n
 It is well known that the Guanine base can base pair with itself by means 
 of Hoogsteen hydrogen bonding\, which can lead to the formation of DNA and
  RNA secondary structures known as G-quadruplex (G4).1 Whilst G4-formation
  has been thoroughly investigated within short genomic sequences\, G-G bas
 e pairing between distal genomic regions have been often overlooked and de
 emed unlikely to happen in vivo. My group has recently discovered the firs
 t human protein (CSB)\, a chromatin remodelling protein\, that can selecti
 vely bind to multimolecular G4-structures (mG4s)\, suggesting that long ra
 nge G-G base pairing can be potentially leveraged to orchestrate chromatin
  architecture.2 More recently\, my group has demonstrated that the repeat 
 expansion of  the hexanucleotide (GGGGCC)n\, which has been linked to the
  neurodegenerative diseases ALS and FTD\, can form solid aggregates in a p
 rotein independent fashion by means of G-G base pairing. We showed a corre
 lation between the emergence of multimolecular G4s (mG4s) formed by the DN
 A (GGGGCC)n repeats and the formation of protein free insoluble aggregates
 . Aggregation is dependent on K+ concentration and repeat-length\, indicat
 ing that G4-formation is essential to observe aggregates. G4-structures we
 re detected in the aggregates by staining with the G4-specific fluorescent
  dye NMM. To reinforce the physiological relevance of our observations\, w
 e characterised the aggregation of RNA (GGGGCC)n\, which is thought to con
 tribute to pathological aggregation in ALS/FTD. We observed that RNA repea
 ts can aggregate at significant lower concentrations compared to DNA\, sug
 gesting that under physiological conditions RNA repeats can aggregate in t
 he absence of any protein. Using patient-derived ALS cell lines\, we valid
 ated our model by observing the same G4-based RNA aggregates in the pathol
 ogical RNA foci that are characteristic of this disease\, suggesting that 
 nucleic acids targeting could be the key to treat neurodegenerative diseas
 es in the future. Our findings constitute the first evidence supporting th
 e formation of multimolecular G4-structures to drive protein-free aggregat
 ion in neurodegenerative diseases\, challenging the current dogmas on the 
 mechanisms responsible of neurodegeneration and associate protein led aggr
 egate formation.3 \n\nSpeaker's biography:\nMarco Di Antonio obtained his 
 MChem from Pavia University (Italy) in 2007 and his PhD in Molecular Scien
 ces from Padua University (Italy) in 2011. He moved to Cambridge Universit
 y in 2011 where he worked as a PDRA under the supervision of Prof Sir Shan
 kar Balasubramanian. In 2015 Marco was promoted to Senior Research Associa
 te\, before being awarded a BBSRC David Phillips Fellowship to start his o
 wn group in 2018.\nMarco moved to Imperial College (Chemistry Department) 
 to start his own group in 2018 as a BBSRC research fellow\, where he was p
 romoted to Advanced Research Fellow in 2021\, as a permanent Lecturer in 2
 022 and as a Senior Lecturer in 2023. His research group works at the inte
 rface between chemistry\, biology and genomics\, with the aim to develop n
 ovel technologies to study cancer and ageing biology from a fresh perspect
 ive.\nMarco was awarded a Lister Institute Prize in 2022\, the Young Inves
 tigator Award in Chemical Biology by the International Chemical Society an
 d 2023 and the runner up prize for the Young Investigator in Medicinal Che
 mistry and Chemical Biology in Academia by EFMC in 2023.\n\n\nLab website:
  https://www.imperial.ac.uk/diantonio-research-group/\n\n 
LOCATION:CE 1 1 https://plan.epfl.ch/?room==CE%201%201
STATUS:CONFIRMED
END:VEVENT
END:VCALENDAR