top of page


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
1 day 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


Smallest Human Virus – Very Dangerous, Very Intelligent
Hepatitis D virus, also called hepatitis delta virus, is one of the strangest human viruses. Its genome is a tiny circular single-stranded RNA of only about 1,700 nucleotides, and it produces essentially one protein in two forms—the small and large hepatitis delta antigens. It does not encode its own enzyme to copy its RNA as most RNA viruses do. It doesn’t produce its own envelope proteins or most of the machinery normally associated with a virus. Instead, it has an extraord
jonlieff
Aug 1324 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
bottom of page
