Lee Hartwell (Fred Hutch): Understanding the Cell Cycle Regulators

Summary

In this engaging conversation, Sue Biggins interviews Lee Hartwell about his groundbreaking work on the cell cycle, which earned him a Nobel Prize in 2001. Hartwell discusses his journey from physics to biology, his choice to study yeast for cell division research, and the discovery of crucial cell cycle checkpoints. He reflects on the creativity needed in scientific exploration, contrasting past and present research funding systems. Hartwell's insights into the conservation of cell cycle genes highlight the fundamental principles of biology and the precision of cellular processes, underscoring the ongoing mysteries yet to be unraveled.

Takeaways

• 😀 Lee Hartwell's pioneering work on the cell cycle earned him the Nobel Prize in Physiology or Medicine in 2001.
• 😀 The cell cycle is a fundamental process in all organisms involving genome and organelle duplication.
• 😀 Hartwell utilized temperature-sensitive mutants in yeast to identify key regulators of the cell cycle, leading to significant discoveries.
• 😀 The cdc28 gene is a master regulatory kinase essential for cell cycle progression and is conserved across various species.
• 😀 Cell cycle checkpoints, like the DNA damage checkpoint, are critical signals that halt the cell cycle when errors occur.
• 😀 Hartwell's interest in biology was sparked by a captivating course on DNA at Caltech, leading him to change his major.
• 😀 The distinction between substrate and signaling models of cell cycle regulation was a critical focus of Hartwell's research.
• 😀 Many CDC genes are conserved, with approximately 50% of yeast genes able to be complemented by human proteins.
• 😀 Hartwell criticized modern scientific funding models for hindering creativity and exploration in research.
• 😀 He reflected on the benefits of a more stable research environment that allows for extended periods of innovation.

Q & A

What key discovery did Lee Hartwell make regarding the cell cycle?

Lee Hartwell identified the CDC genes, which are universal regulators of the cell cycle in various organisms, including yeast, frogs, and humans.

What role does the cdc28 gene play in the cell cycle?

The cdc28 gene is known as the master regulatory kinase that controls the progression of cells through the start of the cell cycle.

How did Hartwell first become interested in science?

Hartwell's interest in science was sparked in high school by a physics teacher who challenged him with difficult problems.

What prompted Hartwell to shift his focus from physics to biology?

A general biology course at Caltech, taught by James Bonner, where the excitement about DNA was emphasized, led Hartwell to change his major to biology.

Why did Hartwell choose to study yeast for his research?

Hartwell chose yeast because he was frustrated with the limitations of studying mammalian cells and wanted a simpler organism for genetic and cell physiology studies.

What is a cell cycle checkpoint, according to Hartwell?

A cell cycle checkpoint is a mechanism that halts cell division when there is an error, allowing for repair before proceeding.

What are the two models of cell cycle regulation that Hartwell distinguished?

Hartwell discussed the substrate model, which suggests that incomplete DNA affects the mitotic spindle, and the signaling model, which posits that internal signals communicate issues to the spindle.

What was the significance of the temperature-sensitive mutants Hartwell studied?

Temperature-sensitive mutants allowed Hartwell to identify essential genes and their roles in various steps of the cell cycle by observing how they behaved under different conditions.

What concerns did Hartwell express about the current research environment?

Hartwell expressed that the current focus on immediate results and defined proposals may hinder creativity and the exploration of new ideas in scientific research.

How did Hartwell and his team validate their findings on cell division mutants?

They used photomicroscopy to observe cell morphology and subsequently developed techniques to stain and visualize the nuclei of the yeast cells.