麻豆传媒色情片

ASBMB Annual Meeting

Understanding cellular function to understand life

Gabriela Contreras
By Gabriela Contreras
March 5, 2021

When Geoffrey Hesketh was growing up in Canada, he loved sciences and math and wanted to be a medical doctor. He became curious about molecular mechanisms after he started volunteering in a biochemistry lab in his second undergraduate year at Queen's University, and he realized that his huge curiosity would be more satisfied working as a scientist than as a physician.

Hesketh-445x450.jpg
Geoffrey Hesketh

Since then, Hesketh has wanted to understand molecular processes, especially those that have evolved for billions of years but that we still are far from understanding, such as cellular nutrient uptake. "Experimentally unravelling a previously obscure or unknown biological function is the ultimate scientific achievement," he said.

Now a postdoctoral fellow in Anne-Claude Gingras' group at the Lunenfeld–Tanenbaum Research Institute of Mount Sinai Hospital in Toronto, Hesketh earned a Ph.D. in biological chemistry at Johns Hopkins School of Medicine in Baltimore and then did a postdoc at the Cambridge Institute for Medical Research.

Hesketh is interested in cellular membrane trafficking and signal transduction. "If you are understanding cell function at the molecular level, you understand life," he said.

Using advanced mass spectrometry and cell biology tools, he studies the molecular mechanisms by which lysosomes control cellular nutrient biology. In nutrient signaling, mechanistic target of rapamycin complex 1, or mTORC1, plays a key role.

"Life is largely driven by the flow of key elements — carbon, hydrogen, nitrogen, oxygen, phosphorus, and sulfur — in different chemical states, from organism to organism," he said.

Hesketh is fascinated by how mTORC1 is fundamental to life, participating in the sensing of the key elements, synthesis and degradation of macromolecules.

Many human diseases originate in cellular dysfunction, so Hesketh believes understanding cellular processes is the way to understand disease. Therefore, as a cellular biologist, he is pursuing his childhood interest in medicine and human diseases.

There's more than one way to activate this protein

Amino acids, sensed by the cell, can be derived through lysosomal degradation of external proteins or via amino acids acquired exogenously through cell surface transporters by macropinocytosis. Mechanistic target of rapamycin complex 1, or mTORC1, is activated by both these sources of amino acids, and mTORC1 function is regulated on the surface of lysosomal system organelles.

Exogenous amino acids are sensed by a mechanism dependent on the Rag guanosine triphosphatases, or GTPases, that control the mTORC activation. Geoffrey Hesketh and collaborators at the Lunenfeld–Tanenbaum Research Institute have demonstrated that lysosome-derived amino acids activate mTORC1 through a Rag GTPase-independent pathway. They have shown that both sources of amino acids activate mTORC1 by two different pathways. Using proximity-dependent biotinylation, known as BioID, and mass spectrometry for protein identification, they designed organelle sensors with which they showed the surface proteomes of late endosomes and lysosomes.

In highly lethal Ras-driven cancers, researchers know that macropinocytosis and lysosomal degradation of external proteins fuel cancer growth, but they do not yet know the mechanisms behind these processes. Hesketh's research results may lead to mechanistic insight into how lysosome-derived nutrients fuel the growth of Ras-driven cancers.

Enjoy reading ASBMB Today?

Become a member to receive the print edition four times a year and the digital edition monthly.

Learn more
Gabriela Contreras
Gabriela Contreras

Gabriela Contreras earned her Ph.D. in biology at Heidelberg University.

Get the latest from ASBMB Today

Enter your email address, and we鈥檒l send you a weekly email with recent articles, interviews and more.

Latest in People

People highlights or most popular articles

Meet the 2025 SOC grant awardees
Outreach

Meet the 2025 SOC grant awardees

Aug. 15, 2025

Five science outreach and communication projects received up to $1,000 from ASBMB to promote the understanding of molecular life science.

Unraveling cancer鈥檚 spaghetti proteins
Profile

Unraveling cancer鈥檚 spaghetti proteins

Aug. 13, 2025

MOSAIC scholar Katie Dunleavy investigates how Aurora kinase A shields oncogene c-MYC from degradation, using cutting-edge techniques to uncover new strategies targeting 鈥渦ndruggable鈥 molecules.

How HCMV hijacks host cells 鈥 and beyond
Profile

How HCMV hijacks host cells 鈥 and beyond

Aug. 12, 2025

Ileana Cristea, an ASBMB Breakthroughs webinar speaker, presented her research on how viruses reprogram cell structure and metabolism to enhance infection and how these mechanisms might link viral infections to cancer and other diseases.

Understanding the lipid link to gene expression in the nucleus
Profile

Understanding the lipid link to gene expression in the nucleus

Aug. 11, 2025

Ray Blind, an ASBMB Breakthroughs speaker, presented his research on how lipids and sugars in the cell nucleus are involved in signaling and gene expression and how these pathways could be targeted to identify therapeutics for diseases like cancer.

In memoriam: William S. Sly
In Memoriam

In memoriam: William S. Sly

Aug. 11, 2025

He served on the 麻豆传媒色情片 and 麻豆传媒色情片 Biology Council in 2005 and 2006 and was an ASBMB member for 35 years.

ASBMB committees welcome new members
Society News

ASBMB committees welcome new members

Aug. 7, 2025

Members joined these committees: Education and Professional Development, Maximizing Access, Meetings, 麻豆传媒色情片, Public Affairs Advisory, Science Outreach and Communication, Student Chapters and Women in Biochemistry and 麻豆传媒色情片 Biology.