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The Life of p53: From Stress Sensor to Guardian of the Genome
p53 is widely known as the “guardian of the genome,” and it is the single most commonly altered protein in human cancer. Yet the modern p53 molecule did not appear all at once with the rise of multicellular animals. Over more than a billion years, it evolved from a simple environmental stress sensor with an on/off switch into one of the most sophisticated information-processing molecules in living cells — a system that gathers signals from dozens of independent pathways and s
jonlieff
2 hours ago22 min read


The Life of mTOR : the Cell's Coordinator of Growth, Energy, Construction, and Survival
mTOR Decision-Making System A Molecular System That Makes Decisions Among the thousands of molecular systems operating inside a human cell, few coordinate as many different activities as mTOR. Its name, mechanistic target of rapamycin, makes it sound like simply another enzyme. Technically, mTOR is a protein kinase: it transfers phosphate groups to other proteins and thereby changes their behavior. But describing mTOR merely as a kinase is like describing a brain as a collect
jonlieff
Sep 1437 min read


The Dance of AMPK
How Molecular Motion Allows Cells to Sense and Communicate About Energy Every living cell must constantly answer the fundamental question whether it has enough energy to grow, or must it conserve resources to survive? The molecule responsible for answering that question is AMPK, the AMP-activated protein kinase. AMPK acts as a cellular energy sensor and regulator that monitors energy levels by responding to changes in the ratios of AMP to ATP and ADP to ATP inside cells. At f
jonlieff
Sep 65 min read


The Dance of mTOR
How Molecular Motion Creates the Master Regulator of Cellular Growth At first glance, mTOR appears to be an enormous molecular machine built for stability. Composed of more than 2,500 amino acids and weighing nearly 300 kilodaltons, it is one of the largest protein kinases in biology. Yet beneath its impressive size lies a remarkable truth: mTOR is never still. Rather than functioning as a rigid enzyme, it exists as an extraordinarily dynamic molecular system whose continual
jonlieff
Sep 45 min read


Intelligent Conversation between Viral RNA and Its Protein
The hepatitis D virus possesses the smallest known human genome—only about 1,680 nucleotides encoding essentially a single protein. Yet from this remarkably limited genetic information emerges a molecular system capable of regulating genome copying, altering its developmental state, exploiting dozens of cellular pathways, and assembling new virus particles with extraordinary precision. The sophistication of HDV does not arise because either its RNA or its protein is independe
jonlieff
Sep 25 min read


Gymnastic RNA with Extremely Condensed Information in the Smallest Human Virus
The hepatitis D virus RNA genome is continuously moving and negotiating interactions with other molecules. It is constantly sampling its own possible shapes while simultaneously engaging in dialogue with proteins that would respond to each of these shapes. These RNA shapes also interact with ions, water, and the three-dimensional architecture of the cell. To understand hepatitis D virus RNA is to appreciate that a single circular molecule of 1,680 nucleotides can simultaneous
jonlieff
Aug 2817 min read


One Small Protein from Smallest Human Virus Does Work of Many
Hepatitis D virus produces essentially one protein—hepatitis delta antigen—in two closely related forms: the 195-amino-acid small antigen and the 214-amino-acid large antigen. Yet from this single gene emerges a molecular system capable of entering the nucleus, organizing viral RNA, exploiting cell RNA polymerases, recruiting genome copying and RNA-processing machinery, undergoing regulatory modifications, switching between genome copying and assembly, binding the envelope pr
jonlieff
Aug 238 min read


A Turing Test for Molecules—Is Hepatitis D virus Intelligent?
It is impossible to exactly define what intelligence would be in a molecule or complex molecular system. The Turing test is used to determine if a machine can match the intelligence of humans, but is inexact. Can we think of a version of a Turing test to consider if hepatitis D virus, the smallest human virus, is intelligent. For the details of hepatitis D virus' very complex lifestyle please refer to the previous post Smallest Human Virus – Very Dangerous, Very Intelligent
jonlieff
Aug 197 min read


AMPK and The Increasing Intelligence of Molecules
From a Primitive Energy Sensor to the Master Guardian of Cellular Energy Long before animals, plants, or the first eukaryotic cells existed, bacteria and archaea already decided the best to use their energy. Every cell continuously judged whether enough ATP was available to build new molecules, or whether scarce resources demanded conservation and repair instead. Early life responded to energy availability, but it did so through many separate, local biochemical sensors rather
jonlieff
Aug 313 min read


mTOR’s Emergence as the Master Cellular Regulator
Increasing Intelligence of mTOR: From a Primitive Survival Kinase to the Master Integrator of Complex Life The story of mTOR shows that biology builds increasingly intelligent molecules not by inventing entirely new molecules, but by continuously expanding the information-processing abilities of existing ones. Today, mTOR (mechanistic Target of Rapamycin) is near the top of the regulatory hierarchy of virtually every human cell. It decides whether cells should grow or shrink,
jonlieff
Jul 266 min read


The Dance of Adenosine, AMP, ATP, and RNA
Adenosine is in perpetual motion. The aromatic adenine ring continually redistributes its electrons, creating changing electrostatic landscapes that influence how it interacts with neighboring molecules. The ribose sugar flexes between slightly different conformations, altering the molecule's three-dimensional geometry. The bond connecting the base to the sugar rotates, allowing adenosine to present different molecular surfaces to enzymes, receptors, and RNA. Around it, layer
jonlieff
Jul 253 min read


What If Atoms Can Think…
If mind exists throughout all of nature, then how would it manifest in the realm of atoms? Would atoms have desires, goals, and plans? What would be their behaviors and personalities? Because their electronic structures are so different, each atom in living matter behaves in remarkably consistent, and different, ways. Therefore it is not difficult to describe them as having distinct personalities. These personalities arise from the fundamental laws of quantum mechanics—th
jonlieff
Jul 186 min read


Is This How Life Began?
Adenine––The First Intelligent Molecule Life did not begin with cells, organs, brains, or nervous systems. Some molecules possessed such extraordinary chemical and physical properties that they repeatedly became the foundation for increasingly complex intelligent biological systems. Among them, one molecule stands out above all others—adenine. Perhaps the reason adenine was the first truly intelligent molecule is the remarkable number of ways it can interact with its surround
jonlieff
Jul 46 min read


A Communication System for All Cells
In 1972, a British pharmacologist named Geoffrey Burnstock published a paper proposing that ATP is released from nerve terminals and acts as a neurotransmitter. The scientific establishment's response was a dismissal. The objections were that as the universal energy currency of all living cells, ATP was too ubiquitous to serve as a signal among neurons––it was everywhere, inside everything. That skepticism delayed a medical revolution by two decades. Burnstock continued wor

Jon Lieff
Jul 25 min read


ATP and Adenosine—Fundamental Cellular Communication Signals
For more than a century, neuroscience has been built around a neuron-centered worldview. The heroes of this story are familiar neurotransmitters: dopamine, serotonin, norepinephrine, acetylcholine, glutamate, and GABA. Textbooks describe neurons communicating across synapses in brain circuits using these specialized chemical messengers. The vast ‘connectome’ network of axons and dendrites was believed to determine mental events. Neurons were viewed as the only true informatio

Jon Lieff
Jun 225 min read


Are Cells Thinking in Light?
For more than a century, biology has largely viewed cellular communication as a chemical process. This chemical view has been very helpful in describing a large number of cellular signaling pathways. However, modern cell biology increasingly reveals a deeper reality. Cells are not simply bags of chemicals. They are highly organized information-processing systems operating across many scales simultaneously. Within every cell, billions of molecules continuously exchange infor

Jon Lieff
Jun 75 min read


Molecular Mind in Cellular Motors 7: The Society of Cell Motors and Tracks
When most people imagine a living cell, they picture a microscopic bag of organic materials. In fact, as described in prior posts, a cell is a vast, organized society whose members constantly communicate, cooperate, negotiate, compete, and adapt to changing conditions. At the center of this society lies a remarkable transportation system: an immense network of molecular tracks, scaffolds, motors, signaling complexes, organelles, and regulatory molecules that continuously exch

Jon Lieff
Jun 55 min read


Molecular Mind in Cellular Motors 6: The Very Talented Dynein Motor
Dynein is a vastly more complex motor than kinesin. It walks along microtubules carrying vesicles, RNA granules, mitochondria, signaling complexes, and even large full chromosomes. It moves the entire cell nucleus during immune cell movement and manages the extraordinarily complex choreography of chromosome separation during cell division. It is a motor with awareness of what each situation requires. Dynein is enormous. Including its essential additional dynactin complex, i

Jon Lieff
May 285 min read


Molecular Mind and Cellular Motors 5: Kinesin Motors––Walking, Communicating Molecular Creatures
Kinesin is an individual cellular motor made of just four protein chains that senses, navigates, makes decisions, and walks with two feet, step by step like a human. It picks up a variety of cargo, such as vesicles, mitochondria, molecular complexes, or messenger RNA and walks, one deliberate step at a time, along a highway of protein cables toward a precise destination. Walking upright on two legs is rare in nature—humans, ostriches, penguins, kangaroos, and a few others—e

Jon Lieff
May 254 min read


Molecular Mind in Cellular Motors 4: The City Inside the Cell––An Infrastructure that Thinks
Many of the cell’s most important functions occur through the actions of a huge, dynamic, complex scaffold that extends throughout the cell. It consists of tracks along which molecular motors walk and carry necessary cargo everywhere in the cell. This scaffold is not made like rigid, passive railroad tracks, but tracks that grow, shrink, and bend—precisely organized, but dynamic and instantly responsive. The tracks stretch from the cell's center outward like spokes, providing

Jon Lieff
May 175 min read
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