Cellular and Molecular Biology for Research

Ahmadreza Gharaeian
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  • MEDICINE
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Cellular and Molecular Biology for Research is the podcast where complex textbooks stop gathering dust and start making sense. Each episode breaks down the dense chapters of cellular and molecular biology—DNA, signaling pathways, protein folding, experimental techniques—into clear explanations for students, early-career researchers, or anyone who wants to actually understand the science instead of just memorizing it. Think of it as your study buddy who reads the heavy stuff, translates the jargon, and hands you the key concepts (with a little less pain and a lot more clarity).

  1. The Synapse Unlocked: From Thumbtacks to Thought: The Electrical Pathway (Section 1)

    6D AGO

    The Synapse Unlocked: From Thumbtacks to Thought: The Electrical Pathway (Section 1)

    We’ve seen how a thumbtack to the foot can trigger an electrical storm in your nerves — but how does that signal jump from one neuron to the next? Welcome to the synapse, the tiny but mighty junction where information changes hands. In this episode, we trace the story from the late 1800s, when scientists first realized neurons don’t just touch — they communicate. Early researchers like Charles Sherrington gave this mysterious meeting point a name, while others debated whether neurons talked through electricity or chemistry. We’ll follow the experiments that settled the score — from Otto Loewi’s famous frog heart experiment that revealed chemical messengers, to Bernard Katz’s work showing how nerve impulses trigger neurotransmitter release, and John Eccles’ discovery that most brain synapses rely on chemical signaling. Today, we know that synaptic transmission is at the heart of everything the nervous system does — from reflexes to memory, emotions to mental illness. Join us as we unpack how these tiny connections create the grand symphony of the brain: how neurotransmitters are made, stored, and released, and how every signal you think, feel, or remember begins at the space between two neurons.

    44 min
  2. None Switch: Unpacking the Action Potential (Section 1)

    FEB 8

    None Switch: Unpacking the Action Potential (Section 1)

    Your brain speaks in electricity — tiny, rapid bursts called action potentials. In this episode, we break down the signal that carries information through your nervous system at lightning speed. Normally, a neuron’s interior is slightly negative compared to the outside — but when an action potential hits, that balance flips in a split second, and the inside becomes positive. This brief electrical surge, also known as a spike or nerve impulse, races along the axon without losing strength. Every thought, movement, and sensation you have depends on the frequency and pattern of these impulses — the brain’s own version of Morse code. Join us as we explore how neurons generate and send these powerful signals, and how a single pulse of electricity becomes the foundation for everything your nervous system does

    50 min
  3. The Biological Battery: How Your Brain's Pumps and Channels Created (Section 1)

    FEB 4

    The Biological Battery: How Your Brain's Pumps and Channels Created (Section 1)

    Ever wonder what’s happening inside your body when you step on a thumbtack and instantly yank your foot away? In this episode, we dive into the electrifying world of your nervous system — literally. From the first spark of pain at your skin to the lightning-fast signals racing up your spinal cord, we unpack how neurons collect, process, and transmit information. You’ll learn how the brain’s communication lines — neurons — send signals not through copper wires, but through charged atoms called ions, and how they’ve evolved a clever trick called the action potential to keep those signals strong and fast. We’ll also uncover the secret “battery” that powers every thought and movement: the resting membrane potential. Join us as we explore how a tiny voltage difference across a cell’s membrane builds the foundation for everything your brain and body can do — from reflexes to reasoning.

    42 min
  4. From Skull Guesswork to Synaptic Gaps: The Epic History of Neuron (Section 1)

    FEB 1

    From Skull Guesswork to Synaptic Gaps: The Epic History of Neuron (Section 1)

    The historical foundations of neuroscience were laid by numerous individuals over many generations. Today, researchers at various levels of analysis and employing diverse technologies are making significant strides in uncovering the brain's functions. The results of these endeavors form the basis of this textbook. The primary aim of neuroscience is to comprehend how nervous systems operate. Valuable insights can often be gained from observing the brain’s activity indirectly. Since behavior reflects brain activity, careful behavioral measurements provide information about the brain's functional capabilities and limitations. Computational models that replicate the brain’s computational properties allow us to explore how such properties emerge. By recording brain waves from the scalp, we can investigate the electrical activity of different brain regions during various behavioral states. Advanced imaging techniques now enable researchers to examine the structure of the living brain in situ, while even more sophisticated methods reveal which brain areas become active under specific conditions. However, despite the advancements in noninvasive methods, these approaches cannot entirely replace direct experimentation with living brain tissue. To interpret remote signals accurately, it is essential to understand how they are generated and their significance. A comprehensive understanding of brain function requires examining its contents—neuroanatomically, neurophysiologically, and neurochemically. The current pace of neuroscience research is remarkable, fueling for new treatments for the many debilitating nervous system disorders affecting millions annually. Yet, despite centuries of progress, including recent decades of advancement, a complete understanding of the brain’s extraordinary abilities remains a distant goal. Nevertheless, this ongoing journey continues to inspire hope and discovery.

    1h 2m
  5. Genomics II: Functional Genomics, Proteomics, and Bioinformatics (CMB final part)

    JAN 28

    Genomics II: Functional Genomics, Proteomics, and Bioinformatics (CMB final part)

    Functional genomics focuses on analyzing the expression of numerous genes. One branch of this field is transcriptomics, which examines transcriptomes—all the RNA transcripts produced by an organism at a specific time. A common approach in transcriptomics involves the creation of DNA microarrays or microchips containing thousands of cDNAs or oligonucleotides. These arrays are hybridized with labeled RNAs (or their corresponding cDNAs) from cells, and the hybridization intensity at each spot indicates the expression level of the corresponding gene. This method enables the simultaneous analysis of the timing and location of expression for multiple genes. Serial Analysis of Gene Expression (SAGE) identifies which genes are expressed in a particular tissue and measures their expression levels. It works by generating short gene-specific tags from cDNAs, ligating them between linkers, and sequencing the ligated tags to determine gene expression and abundance. Cap Analysis of Gene Expression (CAGE) provides similar data but focuses on the 5'-ends of mRNAs, enabling the identification of transcription start sites and aiding in the localization of promoters. High-density transcriptional mapping of entire chromosomes has revealed that most sequences in cytoplasmic polyadenylated RNAs originate from non-exon regions of ten human chromosomes. Additionally, nearly half of the transcription from these chromosomes is nonpolyadenylated. These findings suggest that the majority of stable nuclear and cytoplasmic transcripts derive from regions outside exons, which may explain significant differences between species, such as humans and chimpanzees, whose exons are nearly identical.

    1 hr
  6. Introduction to Genomics: DNA Sequencing on a Genomic Scale (CMB part 22)

    JAN 23

    Introduction to Genomics: DNA Sequencing on a Genomic Scale (CMB part 22)

    Several approaches are available for identifying genes within a large, unsequenced DNA region. One method is the exon trap, which employs a specialized vector to selectively clone exons. Another involves using methylation-sensitive restriction enzymes to locate CpG islands—DNA regions containing unmethylated CpG sequences. Prior to the genomics era, geneticists mapped the Huntington disease gene (HD) to a region near the end of chromosome 4, subsequently using an exon trap to identify the gene itself. Advancements in automated DNA sequencing methods have enabled molecular biologists to determine the base sequences of various organisms, from simple phages and bacteria to yeast, plants, animals, and humans. In the Human Genome Project, much of the mapping work utilized yeast artificial chromosomes (YACs), which are vectors containing a yeast origin of replication, a centromere, and two telomeres. These vectors can accommodate foreign DNA up to 1 million base pairs long, which replicates alongside the YAC. However, due to their superior stability and ease of use, bacterial artificial chromosomes (BACs) became the preferred tool for sequencing. BACs, derived from the F plasmid of E. coli, can accept DNA inserts up to approximately 300 kilobases, with an average insert size of about 150 kilobases. Mapping large genomes, such as the human genome, requires a set of landmarks (markers) to determine the positions of genes. While genes themselves can serve as markers, most markers consist of anonymous DNA segments like RFLPs, VNTRs, STSs (including ESTs), and microsatellites. Restriction fragment length polymorphisms (RFLPs) are variations in the lengths of DNA fragments produced by cutting DNA from different individuals with a restriction enzyme, often caused by the presence or absence of specific restriction sites.

    51 min
  7. Transposition (CMB part 21)

    JAN 20

    Transposition (CMB part 21)

    Transposable elements, also known as transposons, are DNA segments capable of moving from one location to another within the genome. Some transposable elements replicate during the process, leaving one copy in the original position and inserting a new copy at a different site, while others move without replication, vacating the original site entirely. Bacterial transposons can be categorized as follows: (1) insertion sequences, such as IS1, which consist solely of the genes required for transposition and are flanked by inverted terminal repeats; and (2) transposons like Tn3, which resemble insertion sequences but include at least one additional gene, often conferring antibiotic resistance. Eukaryotic transposons exhibit diverse replication strategies. DNA transposons, such as Ds and Ac in maize or the P elements in Drosophila, function similarly to bacterial DNA transposons like Tn3. The immunoglobulin genes in mammals undergo rearrangement through a mechanism analogous to transposition. Vertebrate immune systems generate immense diversity in immunoglobulin production by assembling genes from two or three components selected from a heterogeneous pool. This process, called V(D)J recombination, relies on recombination signal sequences (RSSs) that include a heptamer and a nonamer separated by either 12-bp or 23-bp spacers. Recombination occurs exclusively between a 12 signal and a 23 signal, ensuring the incorporation of only one of each type of coding region into the assembled gene. Key players in human V(D)J recombination are RAG1 and RAG2, which create single-strand nicks in DNA adjacent to a 12 or 23 signal. This triggers a transesterification reaction where the newly formed 3'-hydroxyl group attacks the opposite strand, leading to a break and forming a hairpin at the end of the coding segment.

    35 min
  8. Homologous Recombination (CMB part 20)

    JAN 15

    Homologous Recombination (CMB part 20)

    Homologous recombination is vital for life. In eukaryotic meiosis, it ensures proper separation of homologous chromosomes by locking them together and promotes genetic diversity in offspring by scrambling parental genes. In all life forms, it plays a crucial role in managing DNA damage. In E. coli, homologous recombination via the RecBCD pathway starts with the invasion of duplex DNA by single-stranded DNA from another duplex that has undergone a double-stranded break. This process begins with RecBCD's nuclease and helicase activities, which generate a free end by preferentially nicking DNA at Chi sites. The invading strand is then coated with RecA and SSB. RecA facilitates the pairing of the invading strand with its complementary homologous DNA, forming a D-loop, while SSB enhances recombination by melting secondary structures and preventing RecA from trapping such structures, which could inhibit subsequent strand exchange. Following this, RecBCD likely nicks the D-loop strand, creating a branched intermediate known as a Holliday junction. The RuvA–RuvB helicase catalyzes branch migration, moving the crossover of the Holliday junction to a favorable resolution site. Finally, RuvC resolves the Holliday junction by nicking two of its strands, producing either noncrossover recombinants with heteroduplex patches or two crossover recombinant DNAs. Meiotic recombination in yeast begins with double-stranded breaks (DSBs) created by two Spo11 molecules. These molecules work together to cleave both DNA strands at closely spaced sites through transesterification reactions involving active site tyrosines. This reaction forms covalent bonds between Spo11 and the newly created DSBs. Spo11 is subsequently released.

    27 min
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About

Cellular and Molecular Biology for Research is the podcast where complex textbooks stop gathering dust and start making sense. Each episode breaks down the dense chapters of cellular and molecular biology—DNA, signaling pathways, protein folding, experimental techniques—into clear explanations for students, early-career researchers, or anyone who wants to actually understand the science instead of just memorizing it. Think of it as your study buddy who reads the heavy stuff, translates the jargon, and hands you the key concepts (with a little less pain and a lot more clarity).

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