Prompt Cast
David Sabatini's Groundbreaking Work with mTOR and Rapamycin
TLDR David Sabatini's research journey led to the discovery of mTOR and its interaction with rapamycin, unveiling the intricate role of the mTorque pathway in regulating cellular functions and potential impacts on aging and immunity. Targeting mTOR-1 and exploring amino acid sensing mechanisms could offer insights into longevity and immune function modulation, highlighting the importance of understanding tissue-specific regulation for future advancements in health and fitness.
Timestamped Summary
00:00
David Sabatini discusses his journey in science, focusing on his groundbreaking work with mTOR and rapamycin.
05:21
David Sabatini continued his work on the mTOR protein since his graduate school days, focusing on rapamycin after being intrigued by its potential compared to FK506 in the lab of Sal and Snyder.
10:28
David Sabatini and Stuart Shriver independently discovered mTOR and its interaction with rapamycin and FKBP, leading to the purification of the protein and further research.
15:38
David Sabatini was able to sequence and clone a large cDNA of the mTOR protein by screening libraries of phages, ultimately discovering the complete full-length cDNA through a lucky and innovative approach.
20:54
David Sabatini discovered the gene for Tor and suspected the existence of other proteins in different complexes, leading to the identification of Amptor-containing complexes after years of failed attempts.
26:00
The discovery of a new detergent called CHAPS was a key breakthrough in the purification of interacting proteins, leading to the identification of mTorque 1 and mTorque 2 complexes.
31:21
The mTorque pathway is involved in a wide range of cellular processes, making it a key regulator with the potential to impact cell state and aging through its intricate control over various cellular functions.
37:03
mTOR is involved in various cellular functions beyond anti-aging, impacting processes like sperm production and heart function, but targeting it comes with potential downsides due to its intricate role in cellular immunity and immune system modulation.
42:18
Targeting mTOR-1 itself may not be feasible due to the ATP binding site, so focusing on upstream regulators could allow for modulation of all mTOR-1 substrates with potential tissue specificity, given the complex regulation of mTOR-1 by various factors like nutrients, growth factors, and osmotic changes.
47:18
The mTOR pathway is intricately regulated by the detection of specific amino acids like leucine and arginine, with different organisms having varying sensors for amino acids such as yeast being able to synthesize essential amino acids like leucine.
52:25
Methionine levels drop significantly during fasting, impacting autophagy and longevity, with intermittent dosing of rapamycin potentially offering benefits for longevity and immune function.
57:48
Rapamycin may have cancer cell autonomous effects that could potentially counteract its immunosuppressive properties in terms of cancer development.
01:02:46
The brain has a significant amount of mTOR, and exploring the effects of mTOR modulation on longevity compared to lifestyle modifications like fasting and exercise is of interest.
01:07:51
The future of signal transduction involves understanding the complex interactions of different tissues over time under various conditions, such as fasting, exercise, and obesity, to determine the impact on longevity and which tissues are most crucial.
Categories:
Health & Fitness
