BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Talks.cam//talks.cam.ac.uk//
X-WR-CALNAME:Talks.cam
BEGIN:VEVENT
SUMMARY:Opening doors and boosting energy: cellular programs that enable m
 acrophage tissue infiltration.  - Daria Siekhaus\, ISTA\, Vienna Austria
DTSTART:20230605T133000Z
DTEND:20230605T143000Z
UID:TALK200050@talks.cam.ac.uk
CONTACT:Elena Scarpa
DESCRIPTION:My lab seeks to understand the cellular mechanisms underlying 
 homeostasis\, focusing on the immune system. We are currently examining ho
 w immune cells can move through tissue barriers. This capacity underlies t
 he establishment of tissue resident macrophages that regulate physiology\,
  the capacity of multiple immune cell types to control infection\, and the
  emerging field of immuno-oncology. We utilize the developmental migration
  of Drosophila melanogaster macrophages as they penetrate a region of the 
 embryo as a model\, and extend those findings into higher organisms. I wil
 l talk about two stories illustrating the importance of cellular programs 
 acting both within the surroundings and within the macrophages. We have fo
 und through two-color live imaging\, genetics and optogenetics that initia
 l macrophage infiltration is controlled by the rate of division of the sur
 rounding cells\, providing a powerful new perspective on this process. We 
 have shown that division disassembles the focal adhesions in surrounding t
 issue\, removing a steric hindrance for macrophages to enter. In collabora
 tive work with the Clevers lab\, we have shown that this paradigm holds al
 so for the entry of macrophages into mouse organoids\, underscoring the po
 wer of the fly system to identify broadly applicable principles for invasi
 on. Second I will describe a new program we found acting within Drosophila
  macrophages to enable infiltration by boosting mitochondrial energy produ
 ction. Through genetics\, RNA seq\, metabolomics and direct mitochondrial 
 assays\, we show that a previously unstudied nuclear factor increases ener
 gy production by raising levels of three proteins\; these components coord
 inate metabolic biochemistry and the translation of a subset of mitochondr
 ial proteins due to higher ribosome levels. Two mammalian orthologs of thi
 s nuclear factor can rescue both invasion and mitochondrial defects\, argu
 ing the capacity to positively regulate energy production is conserved\; o
 ne ortholog is strongly linked in GWAS studies to Alzheimer’s. I will al
 so outline our future directions in both areas. 
LOCATION:MRC LMB + online (hybrid)
END:VEVENT
END:VCALENDAR