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Determining the “Minimal Cell”

Determining the “Minimal Cell”. Creating a stripped down model of life?. Life, the canonical “Emergent System”. Luisi, 2002. Approaches to the minimal cell. In progress! Not feasible experimentally (for now). Luisi, 2002. The “minimal characteristics” for Life?.

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Determining the “Minimal Cell”

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  1. Determining the “Minimal Cell” Creating a stripped down model of life?

  2. Life, the canonical “Emergent System” Luisi, 2002

  3. Approaches to the minimal cell In progress! Not feasible experimentally (for now) Luisi, 2002

  4. The “minimal characteristics” for Life? • Homeostasis (implies many components) • Self-reproduction • Evolution • A top-down approach to cell “engineering” simplifies the definition, since the starting point may already be “alive”

  5. Two different top-down strategies • Luisi: Take a lipid membrane bag and start throwing components into it…. • Problems: requires detailed knowledge of cellular function (and interactions) [What do you add?] • Progress: limited to single functions (eg protein synthesis). This is not very different than in vitro • Venter: Strip down a bacterial genome to determine the minimum number of genes needed for survival • Problems: given redundancy, what is “minimal?” • Progress: Estimates now made, proof of concept experimentation

  6. Mycoplasma, the simplest living bacteria • Mycoplasma genitalium, the bacterium with the smallest genome that may be grown in culture. • It is a obligate pathogen in the human urinary tract (it can’t survive elsewhere under normal conditions). This implies it does not require systems that permit adaptation to different environments. • It lacks a cell wall, allowing easier manipulation. • Its genome contains many fewer “redundant” genes than most other bacteria. These encode enzymes with overlapping function; generally one is dispensable.

  7. Glass et al (2006) Essential genes in a minimal bacterium, PNAS 103(2) 425-430 • Studied Mycoplasma genitalium. • Contains 482 protein-coding genes, plus 43 RNA coding genes. • Total genome 580,000 bases (vs 3 billion in human) • Gene function may be blocked by inserting mobile pieces of DNA (transposons) randomly into the genome and looking for survival. • Of the 482 genes, 382 are essential. Another ten genes are sets of 5 pairs of redundant enzyme functions (6%). • Disruption of genes can either slow or accelerate growth.

  8. Other research • Analyze redundancy in more complex bacteria with larger genomes • Transplantation of one bacterial genome into a different species and transformation of the recipient !

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