Lecture Notes: LUCA, The Vagus Nerve, and Protein Folding

LUCA (Last Universal Common Ancestor)

• Concept: LUCA is the last universal ancestor to all modern life on Earth.
  • Includes bacteria, frogs, fish, trees, fungi, and organisms with cells.
• Research: 2024 paper provided a complete picture of LUCA.
  • Holistic understanding involving various scientific disciplines.
• Perspective: LUCA was not the origin of life, but a population rather than a single individual.
  • Many organisms lived during LUCA's time, but their descendants died out.
• Descendants: Two domains of life from LUCA:
  • Prokaryotes: Simple cells like bacteria and archaea.
  • Eukaryotes: Complex cells leading to multicellular life.
• Research Process:
  • Team reconstructed LUCA's genome using 700 bacterial and archaean species.
  • Inferred a gene tree using slowly evolved, conserved genes.
  • LUCA's genome estimated to encode 2,600 proteins.
• LUCA Characteristics:
  • Simple phospholipid membrane, capable of metabolizing hydrogen gas and CO2.
  • Had a CRISPR-Cas system - an immune system to fight viruses.
  • Part of a complex ecosystem, possibly interacting with other organisms.
• Age of LUCA:
  • Estimated to be 4.2 billion years old.
  • Survived soon after earth became habitable.

Vagus Nerve

• Description: Two-way information highway between brain and internal organs.
  • Regulates breathing, heartbeats, hunger (homeostasis).
• Historical Insight: Discovered by Otto Loewi to affect heart rate.
• Research: New connections between brain and immune system revealed.
  • Brain communication with immune system influences inflammatory response.
  • Kevin Tracey's "anti-inflammatory reflex" demonstrated vagus nerve's immune system influence.
• Inflammation Control:
  • Zuker's research identified brainstem neurons controlling inflammation.
  • Potential for new treatments linked to inflammation diseases (e.g., MS, lupus).

Protein Folding and AI

• Importance of Proteins: Essential to life, perform vital functions.
  • Understanding protein structure is crucial to understanding their function.
• Protein Folding Problem:
  • Proteins have numerous folding configurations, yet fold rapidly into functional shapes.
  • Solved using AI by DeepMind's AlphaFold2.
• DeepMind's Breakthrough:
  • Neural network predicts 3D structure from amino acid sequences.
  • High accuracy (99%) in predicting protein structure.
  • Revolutionized protein folding understanding and applications.
• Applications:
  • Protein design for medicine, energy, sustainability.
  • Creation of synthetic genes for novel proteins.
  • Developments in protein interaction prediction tools (AlphaFold3, RoseTTAFold All-Atom).
• Recognition:
  • Nobel Prize awarded to key researchers in 2024 for advances in protein folding.

Conclusion

• Ongoing research and technological advances continue to enhance understanding of life's origins, brain-body interactions, and protein science.
• Future applications of AI promise new scientific breakthroughs and solutions to complex global challenges.