BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Talks.cam//talks.cam.ac.uk//
X-WR-CALNAME:Talks.cam
BEGIN:VEVENT
SUMMARY:Post-transcriptional gene dysregulation in human asthma as determi
 ned by Frac-seq. - Prof. Rocio T. Martinez Nunez\; School of Immunology &a
 mp\; Microbial Sciences\, Kings College\, London
DTSTART:20180727T120000Z
DTEND:20180727T130000Z
UID:TALK106513@talks.cam.ac.uk
CONTACT:Bobbie Claxton
DESCRIPTION:Asthma is a chronic inflammatory disease of the airways affect
 ing 350 million people worldwide and 5.5 million people in the UK. Around 
 5-10% of asthmatics have severe asthma (SA)\, characterised by poor respon
 se to therapy including high dose of inhaled and oral corticosteroids. The
 se patients are at significant risk and represent a major unmet clinical n
 eed. The underlying pathophysiological mechanisms of severe asthma remain 
 inadequately understood\, and little is known about post-transcriptional p
 rocesses taking place in airway cells from patients with asthma. We have c
 ombined Frac-seq with small RNA-sequencing to determine changes at the pos
 t-transcriptional level in bronchial epithelial cells from healthy control
 s and severe asthmatics. Frac-seq consists on subcellular fractionation an
 d RNA-seq\, determining total (cytoplasmic) and polyribosome-bound (engage
 d in translation) mRNA levels. We detected 319 differentially expressed mR
 NAs at the cytoplasmic level and 335 transcripts differentially bound to p
 olyribosomes between health and asthma\, which overlapped in only 15% cand
 idates. Differential gene expression analysis (analysing all mRNAs that ma
 p to a given gene) was able to detect 30% of the changes determined when a
 lternative splicing analysis was performed. The differentially expressed m
 RNAs in both fractions\, cytoplasmic and polyribosome-bound\, mapped to di
 fferent biological pathways\, suggestive of post-transcriptional dysregula
 tion in severe asthma affecting distinct pathophysiological mechanisms. Am
 ongst the differentially expressed microRNAs\, a network of only 6 microRN
 As potentially regulates 50% of the changes detected in mRNA translation a
 nd account for 90% of all cellular microRNA targeting\, with preference fo
 r mRNAs bound to polyribosomes. Modified in bronchial epithelial cells fro
 m healthy donors\, this microRNA hub mimics severe asthma characteristics 
 such as corticosteroid resistance. As microRNAs regulate 50% translational
  changes in SA\, the remaining 50% of changes may be due to dysregulated R
 NA binding proteins (RBPs) in these cells. We are investigating the role t
 hat RNA binding proteins have in the regulation of corticosteroid insensit
 ivity as well as rhinovirus responses. Taken together\, our results demons
 trate the essential importance of assessing post-transcriptional gene expr
 ession and regulation in human asthma\, which we hope will open new paths 
 for therapeutics development.
LOCATION:Babraham - The Cambridge Building\; Kings Hedges Room
END:VEVENT
END:VCALENDAR