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Mechanisms of cell fusion in eukaryotes

Objective

Membrane fusion is a universal process essential inside cells (endoplasmic) and between cells in fertilization and organ formation (exoplasmic). With the exception of SNARE-mediated endoplasmic fusion the proteins that mediate cellular fusion (fusogens) are unknown. Despite many years of research, little is known about the mechanism of cell-cell fusion. Our studies of developmental cell fusion in the nematode C. elegans have led to the discovery of the first family of eukaryotic fusogens (FF). These fusogens, EFF-1 and AFF-1, are type I membrane glycoproteins that are essential for cell fusion and can fuse cells when ectopically expressed on the membranes of C. elegans and heterologous cells.

Our main goals are:
(1) To determine the physicochemical mechanism of cell membrane fusion mediated by FF proteins.
(2) To find the missing fusogens that act in cell fusion events across all kingdoms of life.

We hypothesize that FF proteins fuse membranes by a mechanism analogous to viral or endoplasmic fusogens and that unidentified fusogens fuse cells following the same principles as FF proteins.

Our specific aims are:
AIM 1 Determine the mechanism of FF-mediated cell fusion: A paradigm for cell membrane fusion
AIM 2 Find the sperm-egg fusion proteins (fusogens) in C. elegans
AIM 3 Identify the myoblast fusogens in mammals
AIM 4 Test fusogens using functional cell fusion assays in heterologous systems

Identifying critical domains required for FF fusion, intermediates in membrane remodeling, and atomic structures of FF proteins will advance the fundamental understanding of the mechanisms of eukaryotic cell fusion. We propose to find the Holy Grail of fertilization and mammalian myoblast fusion. We estimate that this project, if successful, will bring a breakthrough to the sperm-egg and muscle fusion fields with potential applications in basic and applied biomedical sciences.

Call for proposal

ERC-2010-AdG_20100317
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Host institution

TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Address
Senate Building Technion City
32000 Haifa
Israel
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 366 486,49
Principal investigator
Benjamin Podbilewicz (Prof.)
Administrative Contact
Mark Davison (Mr.)

Beneficiaries (2)

TECHNION - ISRAEL INSTITUTE OF TECHNOLOGY
Israel
EU contribution
€ 2 366 486,49
Address
Senate Building Technion City
32000 Haifa
Activity type
Higher or Secondary Education Establishments
Principal investigator
Benjamin Podbilewicz (Prof.)
Administrative Contact
Mark Davison (Mr.)
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

Participation ended

United Kingdom
EU contribution
€ 13 513,51
Address
Wellington Square University Offices
OX1 2JD Oxford
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Stephen Conway (Dr.)