Unveiling the mysteries of basic cellular structures

Maya Schuldiner has always been fascinated by the secret dynamics of life’s tiniest components. ‘Cells use molecules like words,’ she says. ‘In the human body, the various parts of the cell need to communicate with each other constantly to create life.’

In 2010, Schuldiner, and her lab at the Weizmann Institute of Science in Israel, set out to explore the molecular structures underlying communication inside cells. They used customised microscopic technology to map out the specific areas (subdomains) that enable communication of a specific organelle, the endoplasmic reticulum (ER). Like organs in the human body, organelles in the cell have specific functions. The ER serves as the transportation system of the eukaryotic cell.

According to Schuldiner, this promised ‘an unprecedented glimpse into this tiny, but highly complex, mechanism of human life.’

Fuelling a paradigm shift in cell biology

By the 1950s, cellular biologists had observed the membrane of the ER under an electron microscope and shown that it can be found extremely close to other organelles. Less known were the intricacies of these subdomains – how they form, what they communicate, and why this is important. Schuldiner was standing at the edge of a decades-long gap between the accepted understanding of basic cellular functioning and what could be seen under a microscope. ‘We know so little about many fundamental cellular processes’, she says. ‘ERC funding has allowed us to create tools to better understand these processes.’

Schuldiner’s lab spent one year designing a tailor-made robotics system. This high-content microscopy technology enabled not only the mapping and tracking of proteins in the ER but also automated data collection, so that experiments could be constantly performed at high throughput, without human intervention.

An interdisciplinary game-changer

At the time of applying for ERC funding, Schuldiner’s lab had been running for about two years. She needed to consolidate the expertise required to handle the equipment and process the rapid data intake. With ERC support, she was able to hire a highly proficient interdisciplinary team of post-docs and researchers in genetics, biochemistry and cell biology.

Over the years, the team systematically mapped the structure of various subdomains in the ER – a first in the field of cellular biology. ‘To visualise and rapidly process high content data was really a game-changer’, admits Schuldiner. The interdisciplinary team was essential to the project’s breakthroughs; namely, a deeper understanding of the structures for cellular communication between organelles. ‘We discovered that this cellular phenomenon is more complex, regulated and important for cell survival and human physiology than previously thought.’

New understanding, new applications

Since the project’s completion in 2015, organelle research has transitioned from a visually poor to a visually rich and exciting domain, ultimately fuelling a new area of cell biology focused on cellular communication in the areas between organelles (‘contact sites’).

The project has also had a transformative effect on Schuldiner personally. ‘ERC support allowed me to crystallise my own view of doing biology as well as my lab’s ability to do world-leading science’, she says. In this vein, visiting researchers from around the world are invited to use her lab’s cutting-edge robotics system to answer their own biological questions. Schuldiner is particularly inspired by consultation requests from rare disease experts, with a view to helping identify the cause and treatment of patients suffering from rare genetic conditions.

Thanks to additional ERC funding, Schuldiner is currently upscaling this high-throughput technology. The aim is to discover new organelle communication structures and better understand the genetic and chemical compounds that modulate cellular functioning.

How the ERC transformed science - interview with Maya Schuldiner

About the researcher

Professor Maya Schuldiner is a member of the Department of Molecular Genetics at the Weizmann Institute of Science in Rehovot, Israel. She completed her undergraduate and graduate studies at the Hebrew University of Jerusalem. She went on to complete her post-doctoral studies at the laboratory of Prof. Jonathan Weissman at University of California, San Francisco, USA. She started her own lab in 2008 at the Weizmann Institute of Science, where she has been committed to studying the functional genomics of organelles. She won an ERC Starting Grant in 2010, and an ERC Consolidator Grant in 2014 and in 2020.