Determining the Minimal Cell

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Determining the Minimal Cell

• Creating a stripped down model of life?

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Life, the canonical Emergent System
Luisi, 2002
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Approaches to the minimal cell
In progress! Not feasible experimentally (fo
r now)
Luisi, 2002
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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

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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

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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 cant 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.

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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.

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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 !