Project highlights

  • Mechanisms by which organisms rapidly respond to sudden environmental changes 
  • Mother senses environmental stress signals to produce stress-resistant progeny 
  • Use of the most recent genome-editing tools, as well as biochemistry, and next-gen sequencing 

Overview

Sudden environmental changes are challenging for the survival of many organisms. Some organisms evolved mechanisms to cope with uncertainty, by sensing the environment and transmitting selected adaptive traits to the next generation. 

We use the nematode Auanema freiburgensis as model to study the mechanisms by which environmental signals sensed by the mother results in the modification of the germline to produce stress-resistant progeny. In this nematode, chemicals produced by nematodes of the same species are used as signals for overcrowding. Thus, by sensing these chemicals, the mother ‘prepares’ the progeny to withstand the lack of food that occurs in overcrowded conditions. The progeny arrests development in the form of larvae, and can survive in the absence of food for several months. Once in a benign environment, the larvae resume development to become self-fertilizing adults.  The main objectives of the project are to identify the chemical nature sensed by the mothers, how the sensory neurons convey the information to the gonad, and how the germline changes result in different kinds of progeny.  

Image of the outline of a person with dots down the middle and descriptive captions to either side.

Figure 1: Conceptual framework. An environmental trigger changes the state of the soma, which sends a signal to modify the germline. 

Host

University of Warwick

Theme

  • Organisms and Ecosystems

Supervisors

Project investigator

Andre Pires da Silva (University of Warwick; [email protected])

Co-investigators

Robin Allaby (University of Warwick; [email protected])

How to apply

Methodology

Chemicals will be isolated from nematode cultures and tested for their influence on the sex determination and stress-resistance in the F1 generation. To identify the neuron sensing the chemicals, single cells will be tested by killing them with the use of a laser microbeam. The nature of the communication signal between the neuron and the germline will be tested by performing gene knockouts using the genome editing technology. Changes in the germline upon neuronal signal will be tested using immunoprecipitation with antibodies recognizing histone modification markers. 

Training and skills

Students will be awarded CENTA2 Training Credits (CTCs) for participation in CENTA2-provided and ‘free choice’ external training. One CTC equates to 1⁄2 day session and students must accrue 100 CTCs across the three years of their PhD.  

Students will learn to use the latest genome editing technologies (CRISPR-Cas9) to inactivate gene function and to tag genes to visualize their time and site of expression. Furthermore, students will acquire skills in bioinformatics (learn how to code in Unix and R), how to ablate single cells and immunocytochemistry. In addition, students will learn how to organize and execute their experiments in a timely fashion, how to document experiments, prepare presentations, write professional articles and work in a team. Many of those skills are transferable to other disciplines and professions.   

Partners and collaboration

The chemical characterization of the signals produced by nematodes will be in collaboration with the chemist Frank C. Schroeder at Cornel University (USA). The characterization of gene expression changes will be performed with the collaboration with the laboratory of Oded Rechavi at Tel-Aviv University (Israel). 

Further details

Further details on how to contact the supervisor for this project and how to apply for this project can be found here: 

For any enquiries related to this project please contact Andre Pires da Silva, University of Warwick , email: [email protected].

To apply to this project: 

  • You must include a CENTA studentship application form, downloadable from: CENTA Studentship Application Form 2024. 
  • You must include a CV with the names of at least two referees (preferably three) who can comment on your academic abilities. 
  • Please submit your application and complete the host institution application process via: https://warwick.ac.uk/fac/sci/lifesci/study/pgr/studentships/nerccenta/ Complete the online application form – selecting course code P-C1PB (Life Sciences PhD); from here you will be taken through to another screen where you can select your desired project. Please enter “NERC studentship” in the Finance section and add Nikki Glover, [email protected] as the scholarship contact. Please also complete the CENTA application form 2024  and submit via email to [email protected].  Please quote 2024-W2 when completing the application form. 
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Applications must be submitted by 23:59 GMT on Wednesday 10th January 2024. 

Further reading

  1. Pembrey, M.E., Bygren, L.O., Kaati, G., Edvinsson, S., Northstone, K., Sjostrom, M., Golding, J., and Team, A.S. (2006). Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet 14, 159-166.
  2. Grossniklaus, U., Kelly, W.G., Ferguson-Smith, A.C., Pembrey, M., and Lindquist, S. (2013). Transgenerational epigenetic inheritance: how important is it? Nat Rev Genet 14, 228-235.
  3. Cossetti, C., Lugini, L., Astrologo, L., Saggio, I., Fais, S., and Spadafora, C. (2014). Soma-to-germline transmission of RNA in mice xenografted with human tumour cells: possible transport by exosomes. PLoS One 9, e101629.
  4. Dias, B.G., and Ressler, K.J. (2014). Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci 17, 89-96.
  5. Kaati, G., Bygren, L.O., and Edvinsson, S. (2002). Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents’ slow growth period. Eur J Hum Genet 10, 682-688.
  6. Sharma, A. (2015). Transgenerational epigenetic inheritance: resolving uncertainty and evolving biology. Biomol Concepts 6, 87-103.
  7. Devanapally, S., Ravikumar, S., and Jose, A.M. (2015). Double-stranded RNA made in C. elegans neurons can enter the germline and cause transgenerational gene silencing. PNAS 112, 2133-2138.
  8. Heard, E., and Martienssen, R.A. (2014). Transgenerational epigenetic inheritance: myths and mechanisms. Cell 157, 95-109.
  9. Rechavi, O., Houri-Ze’evi, L., Anava, S., Goh, W.S., Kerk, S.Y., Hannon, G.J., and Hobert, O. (2014). Starvation-induced transgenerational inheritance of small RNAs in C. elegans. Cell 158, 277-287.
  10. Rechavi, O., Minevich, G., and Hobert, O. (2011). Transgenerational inheritance of an acquired small RNA-based antiviral response in C. elegans. Cell 147, 1248-1256.
  11. Greer, E.L., Beese-Sims, S.E., Brookes, E., Spadafora, R., Zhu, Y., Rothbart, S.B., Aristizabal-Corrales, D., Chen, S., Badeaux, A.I., Jin, Q., et al. (2014). A histone methylation network regulates transgenerational epigenetic memory in C. elegans. Cell Rep 7, 113-126.
  12. Edison, A.S. (2009). Caenorhabditis elegans pheromones regulate multiple complex behaviors. Curr Opin Neurobiol 19, 378-388.
  13. Schroeder, F.C. (2015). Modular assembly of primary metabolic building blocks: a chemical language in C. elegans. Chem Biol 22, 7-16.
  14. Kanzaki, N., Kiontke, K., Tanaka, R., Hirooka, Y., Schwarz, A., Muller-Reichert, T., Chaudhuri, J., and Pires-daSilva, A. (2017). Description of two three-gendered nematode species in the new genus Auanema (Rhabditina) that are models for reproductive mode evolution. Sci Rep 7, 11135.