# Outline

1.  Beyond the Central Dogma
2.  Transcription Factors
3.  Pseudomonas Aeruginosa
4.  Proposal

# **Beyond the Central Dogma**

## Levels of Organization

- Hierarchical structure
- Increasing in complexity
  - Each "layer" composed of the previous level's basic unit

### Biosphere

::::: columns
::: {.column width="40%"}
Remarks:

All of the world's ecosystem
:::

::: {.column width="60%"}
Example:

Earth
:::
:::::

![](images/paste-1.png){fig-align="center"}

### Ecosystem

::::: columns
::: {.column width="40%"}
Remarks:

Interacting community of organisms (tree, people, fungi, etc...)
:::

::: {.column width="60%"}
Example:

Forest
:::
:::::

![](images/paste-2.png){fig-align="center"}

### Organism

::::: columns
::: {.column width="40%"}
Remarks:

Individual in a species
:::

::: {.column width="60%"}
Example:

Human
:::
:::::

![](images/paste-3.png){fig-align="center"}

### Organ

::::: columns
::: {.column width="40%"}
Remarks:

Group of tissues that carry out functions
:::

::: {.column width="60%"}
Example:

The eye
:::
:::::

![](images/paste-6.png){fig-align="center"}

### Tissue

::::: columns
::: {.column width="40%"}
Remarks:

Homogeneous group of cells
:::

::: {.column width="60%"}
Example:

Retina
:::
:::::

![](images/paste-7.png){fig-align="center"}

### Cells

::::: columns
::: {.column width="40%"}
Remarks:

Composed of organelles
:::

::: {.column width="60%"}
Example:

Photoreceptors
:::
:::::

![](images/paste-8.png){fig-align="center"}

### Organelles

::::: columns
::: {.column width="40%"}
Remarks:

Composed of molecules
:::

::: {.column width="60%"}
Example:

Nuclei
:::
:::::

![](images/paste-9.png){fig-align="center"}

### Molecules

::::: columns
::: {.column width="40%"}
Remarks:

Composed of atoms
:::

::: {.column width="60%"}
Example:

Nucleic acids
:::
:::::

![](images/paste-10.png){fig-align="center"}

## Hierarchical Causation

![Bottom-up and top-down causation from the quantum level up to the organism level and down again.](images/paste-4.png){fig-align="center"}

### Causation at the Molecular level

![Systems biology view of upward and downward causation in biology as a feedback diagram.](images/paste-5.png)

::: notes
While the upward causation is well known (black links), some of major downward causation (blue links) elements include TFs, epigenetic regulators, reverse transcriptases, DNA_polymerases † , and recombinases.
:::

## Beyond the Central Dogma

- The same genome under different control lead to differenct protome
- Some control mechanisms:
  - External signals: Environmental cues lead to genetic change
  - Epigenetic: Cell chemically lock gene expression
  - Transcription Factors: Protein influences back DNA

### Chimpanzee

- 98.8% genome shared with humans
- Difference lies primarily in regulatory and non-coding regions

![](images/paste-12.png)

### Cell Differentiation

- Process where unspecialized stem cells become specialized cells
- Controlled by selectively switching specific genes on or off
  - Leading to unique patterns of gene expression

![](images/paste-11.png)

# **Transcription Factors** (TF)

## Behavior & Mechanism

- Proteins that bind specific DNA sequences to activate or repress transcription
  - key determinant in whether the gene expression
- Very diverse
- Can bind to the DNA itself, or the directly to the RNA polymerase.

## (Many) Responsibilities

- Common way in which cell repond to extracellular information
  - environmental stimuli
  - signals from other cells
- Regulate other transcription factors
  - cascade: primary TF promote secondary TF, which in turn promote the third, and so on.
  - a TF can hold bindings sites for other TF
- Control back the own gene responsible for their own transcription

# **Pseudomonas Aeruginosa** (PA)

## Quick Facts

- Gram-negative, motile, aerobic rod
- Ubiquitous — soil, water, plants, hospital surfaces, human host
- One of the top three causes of opportunistic human infections (WHO critical priority)
- Intrinsically resistant to many antibiotics and disinfectants

![](images/paste-13.png)

## Exceptionally Complex Regulatory Network

- 9% of the genome dedicated to regulation.
- Transcriptional Regulators
- Post-transcriptional regulators,
- Quorum Sensing (QS)

![](images/paste-14.png)

## PA as Biocontrol agent

- Direct Pathogen suppression [@li2024]
- Induced Systemic Resistance [@yu2022] [@demeyer1999]
- Growth Promotion [@thammasittirong2025]

## Phenotype-Genotype discordance

- PA clinical and environmental (biocontrol/agricultural) strains show significant genetic overlap, with studies indicating they share approximately 62% to over 90% of their virulence genes [@arocamolina2024]
- What genes are expressed under which circumstance depend largely on its regulatory network

# Proposal

## The question

- Predicting whether a PA strain is a safe biocontrol agent or a latent pathogen from its TF profile.
- Output vectors:
  - Biocontrol efficacy
  - Virulence risk

## Data Collection

- PA has substantial transcriptomic databases, however:
  - Most are clinical isolates only
  - Virtually no biocontrol data is publicly available

## The Challenge

- Literature extraction
- Measure them yourself

## Citations