When an elephant collapsed and died just outside Broughty Ferry in 1706, local surgeon Patrick Blair decided to dissect it. In doing so, he made a name for himself in British scientific circles. But the expired elephant had travelled a long way before it reached the shores of the Tay – touring more than half-way round Europe for two decades.

Andy Drummond, author of the book Elephantina, now presents for the very first time the full and unexpurgated history of the ‘Dundee Elephant’.

Expect to be entertained by rope-dancers and gun-toting elephants! Swoon at the sight of 260 bones and a slippery pile of internal organs! Be appalled by the behaviour of London impresarios and the deviousness of Edinburgh lawyers! Applaud the achievements of Patrick Blair, honoured son of Dundee!

This free talk takes place in the D'Arcy Thompson Zoology Museum. Please enter via the main front entrance of the Carnelley Building (the big wooden door) where you will be met and directed to the museum. Please note that latecomers may not be admitted.

Abstract

Efforts to measure precipitation extend back into history for more than 500 years, and to date remain challenging owing to the effects of wind, snow and local variability in precipitation-generating processes. Errors in precipitation amounts can easily exceed 20%, and prominent inconsistencies are known where catchment runoff appears to exceed precipitation inputs, even without allowing for evaporative losses. One solution to the unreliability of precipitation data is to simply avoid precipitation estimates altogether and use runoff data instead, but this does a disservice to scientists who may wish to see closure of the water balance, may need to undertake design studies (e.g. requiring probable maximum flood estimates) or to better understand hydrological processes in a changing environment. The presentation reviews insights gained from analysis of 100+ years of rainfall data and evaluates the prospects for producing rainfall observations which are fit for purpose.

Hosts: Karim Labib and John Rouse

Venue: MSI Small Lecture Theatre, SLS

Abstract:

Exonuclease EXO1 performs multiple roles in DNA replication and DNA damage repair (DDR). However, EXO1 loss is well-tolerated, suggesting the existence of compensatory mechanisms that could be exploited in DDR-deficient cancers. Using CRISPR screening, we find EXO1 loss as synthetic lethal with many DDR genes somatically inactivated in cancers, including Fanconi Anaemia (FA) pathway and BRCA1-A complex genes. We also identify the spliceosome factor and tumour suppressor ZRSR2 as synthetic lethal with loss of EXO1 and show that ZRSR2-deficient cells are attenuated for FA-pathway activation, exhibiting cisplatin sensitivity and radial chromosome formation, which we attribute to discreet splicing defects that compromise FA pathway genes. Finally, FA or ZRSR2 deficiencies depend on EXO1 nuclease activity and can be potentiated in combination with PARP inhibitors or ionizing radiation. These findings implicate EXO1 as a synthetic lethal vulnerability and promising drug target in a broad spectrum of DDR-deficient cancers unaddressed by current therapies.

 Bio:

Marija is originally from Zagreb, Croatia, where she obtained her Diploma/MSc in Molecular Biology from the University of Zagreb. Marija did her PhD in the lab of Professor Karim Labib, starting at the Cancer Research UK Manchester Institute and moving with Karim’s lab to MRC PPU in the final year of her PhD. Marija’s PhD thesis was on the mechanism of CMG disassembly at the end of chromosome replication and identifying Cdc48/p97 as the factor driving the disassembly. For her PhD work Marija won the Cancer Research UK Pontecorvo Prize and University of Dundee’s Howard Elder Prize for Cancer Research. Marija then went to do her postdoc in the lab of Simon Boulton at The Francis Crick Institute, where she has since worked on double strand break repair metabolism, telomere maintenance metabolism as well as investigation of DNA damage repair pathways in the context of cancer by using CRISPR screening approaches. Her main recent focus has been the genetics of exonuclease EXO1 and defining EXO1 as a promising cancer therapy target, and on which she has been continuing her work as Crick Early Career Translation Fellow.