Introduction to Microbiology¶

Computational bioengineering requires a clear conceptual map of biological systems before we can attempt to model them. Distinguishing the different biological scales and understanding the unique properties of microorganisms is essential.

Biology vs. Microbiology¶

Biology: studies life in all its forms, from molecular mechanisms to ecosystems.
Microbiology: focuses on microorganisms (bacteria, archaea, viruses, unicellular eukaryotes).

Why does this matter in computational bioengineering?¶

Biology provides the general principles (e.g., DNA structure, metabolism, evolution).
Microbiology provides experimental models that are computationally tractable because bacteria (like E. coli) are simpler, grow fast, and have well‑characterized genomes and molecular pathways.

Prokaryotic vs. Eukaryotic Cells¶

Cells can be divided into two fundamental types: Prokaryotic cells (such as Bacteria, Archaea, etc.) and Eukaryotic cells (Animals, Plants, etc.).

In simple words, a prokaryotic cell is like a small studio apartment where everything happens in one room, while a eukaryotic cell is like a large house with many rooms, each with a special function.

Feature	Prokaryotic Cells (Bacteria, Archaea)	Eukaryotic Cells (Animals, Plants, Fungi, Protists)
Nucleus	No nucleus; DNA in nucleoid	True nucleus with nuclear membrane
Size	Small: 1–5 µm	Larger: 10–100 µm
Organelles	None (no membrane-bound organelles)	Many: mitochondria, ER, Golgi, lysosomes
Genetic Material	Circular DNA chromosome + plasmids	Linear DNA with histones, organized as chromatin
Gene Expression	Coupled transcription–translation in cytoplasm	Decoupled: transcription in nucleus, translation in cytoplasm
Examples	E. coli, Bacillus subtilis, Mycobacterium tuberculosis	Human cells, yeast (Saccharomyces cerevisiae), plant cells

1. Nucleus¶

Prokaryotic cells: They don’t have a nucleus. Their DNA floats freely in a part of the cell called the nucleoid.
Eukaryotic cells: They have a true nucleus, which is a membrane-bound “control center” that stores DNA and directs all cell activities, like the brain of the cell.

2. Size¶

Prokaryotic cells: Small, usually 1–5 micrometers (µm).
Eukaryotic cells: Bigger, usually 10–100 µm.

3. Organelles¶

Prokaryotic cells: Very simple, with no membrane-bound organelles. Everything happens in the same space.
Eukaryotic cells: Complex, with many specialized compartments called organelles, each performing a specific function:
- Mitochondria: produce energy for the cell
- Endoplasmic reticulum (ER): makes proteins and fats
- Golgi apparatus: packages and ships proteins and other molecules
- Lysosomes: break down waste and recycle materials

4. Genetic Material¶

Prokaryotic cells: DNA is circular and may also have plasmids (small extra DNA rings).
Eukaryotic cells: DNA is linear and wrapped around proteins called histones, organized in a structure called chromatin.

5. Gene Expression¶

Prokaryotic cells: DNA is transcribed and translated at the same time in the cytoplasm, which allows the cell to make proteins quickly.
Eukaryotic cells: DNA is transcribed in the nucleus and translated in the cytoplasm. This separation allows for more control but is slower.

The Central Dogma¶

The central dogma of molecular biology describes how genetic information flows:

DNA → RNA → Protein

This represents the basic roadmap of how cells turn genetic information into functional molecules. DNA is made up of genes, which are sequences of nucleotides that store the instructions for building proteins. Structurally, DNA is double-stranded, while RNA is usually single-stranded and can travel from the nucleus to the ribosome.

Why don’t cells synthesize proteins directly from DNA?
DNA cannot leave the nucleus in eukaryotes, so RNA acts as a “temporary copy” of the gene, carrying the instructions safely to the ribosome where proteins are made. Even in prokaryotes, RNA is used as a temporary copy of DNA for several reasons:

Regulation: mRNA levels can be quickly adjusted to control protein production.
Multiple copies: Many ribosomes can translate the same mRNA simultaneously, speeding up protein synthesis.
DNA protection: Using mRNA reduces the risk of damaging the original DNA.
Coordination: Polycistronic mRNAs allow multiple genes to be expressed together efficiently (e.g., operons).

Step 1: Transcription¶

Watch Video

DNA → mRNA (through RNA polymerase)

The objective of transcription is to read DNA and synthesize mRNA, which contains the "recipe" (genetic instructions in the form of codons) to build one or more proteins.

During transcription, there are four important actors:

DNA: made up of genes
RNA polymerase: the key enzyme that makes an RNA copy of a gene. It does not need primers, but it does require a promoter, a DNA sequence “upstream” of a gene that signals where transcription should begin.
Sigma factors: proteins that guide RNA polymerase to the right promoters and are highly task-specific (e.g., σ70 for housekeeping genes, σ32 during heat shock).
mRNA: synthesized during this step. In prokaryotes, mRNA can be polycistronic, encoding multiple proteins from a single transcript (common in operons, e.g., lac operon).

Step 2: Translation¶

Watch Video

mRNA → Protein (through ribosomes)

The objective of translation is to read the mRNA “recipe” and assemble the corresponding protein, linking amino acids in the correct order (each codon specifies one amino acid). In prokaryotes, translation can occur while transcription is still ongoing; this is called coupled transcription–translation, which allows the cell to respond quickly to environmental changes.

During translation, there are four main elements:

mRNA: carries genetic instructions from DNA in the form of codons (three-nucleotide sequences), specific for each amino acid.
Ribosomes: the cell’s protein factories, which read the codons on mRNA and catalyze peptide bond formation to link amino acids in order. Ribosomes bind to the Shine-Dalgarno sequence on the mRNA to start translation.
tRNA (transfer RNA): acts like a delivery truck carrying the correct amino acid to the ribosome. Each tRNA has an anticodon that matches a codon on the mRNA, ensuring the correct amino acid is added to the growing polypeptide chain.
Protein chain (polypeptide): synthesized by the ribosome as it links amino acids together. Polypeptides must fold into their functional three-dimensional structure, sometimes with the help of chaperones, to become usable by the cell.

Step 3: Protein Folding & Function¶

Objective: Convert the linear polypeptide chain into a functional, active protein that can perform cellular tasks.

Key points:

Folding: Polypeptides fold into specific 3D structures determined by the sequence of amino acids.
Chaperones: Some proteins require helper proteins called chaperones to fold correctly and avoid misfolding.
Functional roles of proteins:
- Enzymes: catalyze biochemical reactions
- Structural proteins: maintain cell shape and integrity
- Regulatory proteins: control gene expression and signaling pathways
- Transport proteins: move molecules across membranes
Misfolded proteins can be degraded by the cell to prevent damage.

In summary, the central dogma in prokaryotes ensures rapid, efficient production of functional proteins from DNA, with transcription, translation, and folding tightly coordinated to respond to environmental changes.