Our Research

 

Functional genomics of organelles One of the hallmarks of eukaryotic cells is the presence of membrane-enclosed organelles that create optimized environments best suited for promoting the various chemical reactions required to sustain life. Although more than 15 years have passed since the publication of the Saccharomyces cerevisiae genome sequence, over 30% of the proteins that reside in its organelles have never been studied and more than half of them do not have a known biochemical function. Most of these proteins are conserved all the way to humans and some have been implicated in diseases. One of the great challenges of the post-genomic era is, therefore, to use novel methodologies to fill in these gaps in our knowledge, to uncover the functions of these unstudied proteins, and to delineate pathways and networks that enable the function and communication of these organelles. Our lab is dedicated to uncovering novel functions for yeast organellar proteins. We do this by employing a wide variety of high throughput screening techniques complemented by dedicated cell biological, genetic and biochemical follow ups.

 


 

 

Below is more detailed information about our projects:

Uncovering  biogenesis                     mechanisms of contact sites

Yael Elbaz

Inter-organelle communication is a fundamental, yet poorly understood aspect of cellular organization. Yael is interested in mapping the proteins mediating and operating in organelle contact sites as well as understanding the cellular processes taking place in them.

 



 

Using systematic screening approaches to discover  functions of  uncharacterized ER proteins

Yifat Cohen

Yifat is using a variety of systematic approaches, such as physical interaction maps and high content screens, in order to uncover the function of an uncharacterized ATPase that is essential for ER function.

 

Defining the proteins required for efficient translocation into the ER

Tslil Ast

Tslil focuses on the various translocation pathways of proteins into the endoplasmic reticulum. She is uncovering novel cellular factors important for efficient translocation as well as quality control when this insertion doesn’t take place.

 


 

Understanding the mechanisms of formation and elimination of intracellular protein inclusions

Ofer Moldavski

Ofer is interested in discovering new proteins that enable yeast to clear protein aggregates and inclusion-bodies from the cytosol following stress. He focuses on proteins that mediate interaction of these aggregates with cellular organelles.

 

Uncovering novel mRNA elements involved in RNA localization

Ido Yoffe

Ido is interested in regulatory elements within mRNAs. He has built synthetic reporter libraries to investigate and uncover hidden features within 3'UTRs and introns of yeast genes. These libraries are also used to uncover novel protein factors mediating specificity in mRNA maturation.

 




Creation of a dynamic cellular protein localization atlas

Michal Breker

Michal is characterizing changes in protein localization and levels during yeast stress responses and in different genetic backgrounds. She is doing this using our microscopic platform that is both high-throughput and enables single-cell analysis.

"You can see her results in the Loqate database webpage"

 

Chracterizing the role of organellar proteins in cellular aging

Shai Fuchs

Shai studies senescence and aging using yeast in stationary phase as a model. He developed a high-throughput approach for cytometry-based measurement of longevity and is systematically screening for organellar proteins affecting senescence.

 

 

Characterization of novel elements in the SRP independent translocation pathway

Naama Aviram

Naama studies the Signal Recognition Particle (SRP) Independent pathway of protein translocation into the ER. Using systematic genetic screens she has uncovered new proteins required for translocation through this pathway.

 

 


The high-throughput setup in our lab

In our lab we have set up a high content screening platform yielding high-resolution images of yeast for analysis. The setup consists of a ScanR inverted epifluorescence microscope with an autofocus system and an automated stage (Olympus) coupled to a high-resolution, cooled, CCD camera with an extremely high quantum yield and small pixel size (necessary for good resolution within the very small yeast cell). Our microscope is connected via a robotic Hamilton SWAP arm to a Liquid handler. This setup allows us to visualize the sub cellular localization of a protein in more than 6000 different conditions or genetic backgrounds (equivalent to an entire yeast deletion library) in a couple of days while obtaining high-resolution images. Since this approach is fully automated we can collect single cell information on hundreds of cells per sample enabling population statistics or single cell analysis.