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Neuronal reprogramming of the germline

Principal Supervisor: Dr Andre Pires da Silva, School of Life Sciences

Co-supervisor: Jose Gutierrez-Marcos

PhD project title: Neuronal reprogramming of the germline

University of Registration: University of Warwick

Project outline:

In animals, information usually cannot pass from the soma to the germline. Known as the ‘Weismann barrier’, this has been a dogma in Biology ever since its initial report in 1893. The initial report was based on experiments performed by an evolutionary biologist named August Weismann, who repeatedly shortened the tails of mice for five generations. Even after so many generations, he did not find mice that were born with a rudimentary or missing tail. The implications of his finding were fundamental, namely that phenotypes acquired by the somatic (body) cells cannot be inherited. Instead, only the germ cells (germline) contain heritable information.

Surprisingly, several recent reports indicate that the Weismann barrier can be breached in several organisms, including mammals. In mice, metabolic alterations in the father is passed to the following generation through small RNAs in the sperm. In humans, epidemiological studies, suggest that dietary distress in ancestral generations can affect the health of subsequent generations. However, it is very difficult to prove causation in human studies, and in many animal models confounding factors make interpretation of the results very difficult.

We will use a roundworm model system that facilitates the study of soma to germline transmission because it is very easy to keep in the laboratory, reproduces in great numbers, and displays unequivocal responses to the environment over a generation. The model, a new species of roundworm, senses the environment to produce two

types of offspring. If the environment is benign, the mother produces juveniles that develop rapidly into stress-sensitive larvae. However, if the environment is unfavorable for growth, the mothers produce juveniles that arrest their development into a stress-resistant form.

Roundworms sense the environment through chemical signals. We have preliminary evidence for the nature of the chemical signal that interacts with the soma, as well as the neuronal cell reacting to this stimulus. This is significant because it provides a level of detail that has not been possible with other models. Thus, we are well positioned to uncover the molecular details of how a specific neuron communicates with the germline, and how those genes are translated into different traits into the following generation. By characterizing the molecular basis of how environmental signals alter the germline, we can in the future test whether similar mechanisms are present in other organisms.

BBSRC Strategic Research Priority: Molecules, cells and systems

Techniques that will be undertaken during the project:

  • gene editing tools to generated mutant nematodes (e.g., CRISPR/Cas9)
  • generation of transgenic nematodes (e.g., tagging of specific proteins with fluorescent markers)
  • microscopy (e.g., time lapse videos, confocal microscopy)
  • bioinformatics (e.g., writing scripts in Unix, R and Python)
  • mathematical modelling (R, Python)

Contact: Dr Andre Pires da Silva, University of Warwick