Dr David Weinkove
C. elegans research lab
We study the nematode worm Caenorhabditis elegans. This model system provides controlled conditions and large numbers of animals to understand basic biological processes such as ageing and host:microbe interactions using genetics, biochemistry and microscopy.
Bacteria and Ageing
Animals have co-evolved with microbes, so understanding these interactions is vital to understanding animal biology. The human gut microbiota is an area of intense study but it is difficult to do controlled experiments
In the lab, C. elegans is cultured with the live bacteria Escherichia coli as a food source. We study both E. coli and C. elegans to understand this animal: microbe interaction.
Inhibiting folate synthesis in E. coli slows ageing in C. elegans without slowing the growth of the bacteria or the worm. E. coli synthesises more folate than it needs for growth and we think that this excess folate causes the bacteria to be detrimental to the animal.
We are testing this hypothesis, investigating molecular mechanisms and exploring relevance to human microbiota and health.
Folic acid supplements
We have found that folic acid, the synthetic compound used to prevent folate deficiency is taken up by C. elegans via E. coli, in a pathway that relies of folic acid breakdown. We found that folic acid supplements contain breakdown products that would allow this path to be taken in humans. Blog
Automated analysis of ageing
Together with Chris Saunter we have invented a way to automate measurements of healthspan in many large populations of worms simultaneously. We organised an international workshop in this field and plan a spinout company to test drugs and other interventions to prolong healthspan
Making therapeutic proteins
In another project, we are using C. elegans to make recombinant proteins from parasitic nematodes that could be used to treat diseases of the immune system such as asthma or rheumatoid arthritis. The intention is to enable translation to a therapy and reduce the use of lab rodents. See video
Current lab members (in order of appearance)
Past lab members (other than 3rd year undergraduate project students)
Andrea Bender, Marjanne Bourgois, James Pauw, Nikolin Oberleitner, Gonçalo Correia, Natasha Chetina, Inna Feyst, Harry Blandy, Marta Cipinska, David Bradley, Shona Lee, Noel Helliwell, Jie Jia, Razan Bakheet, Daniel Weintraub, Bhupinder Virk, Lucy Lancaster, Zoe Walmsley, Giulia Zavagno, Claire Maynard, Fiona Hair
Department of Biosciences
- C. elegans
- E. coli
- Host:microbe interactions
- Microbial folates
- Lundquist, Mark R., Goncalves, Marcus D., Loughran, Ryan M., Possik, Elite, Vijayaraghavan, Tarika, Yang, Annan, Pauli, Chantal, Ravi, Archna, Verma, Akanksha, Yang, Zhiwei, Johnson, Jared L., Wong, Jenny C.Y., Ma, Yilun, Hwang, Katie Seo-Kyoung, Weinkove, David, Divecha, Nullin, Asara, John M., Elemento, Olivier, Rubin, Mark A., Kimmelman, Alec C., Pause, Arnim, Cantley, Lewis C. & Emerling, Brooke M. (2018). Phosphatidylinositol-5-Phosphate 4-Kinases Regulate Cellular Lipid Metabolism By Facilitating Autophagy. Molecular Cell 70(3): 531-544.e9.
- Hastings, Janna, Mains, Abraham, Artal-Sanz, Marta, Bergmann, Sven, Braeckman, Bart P., Bundy, Jake, Cabreiro, Filipe, Dobson, Paul, Ebert, Paul, Hattwell, Jake, Hefzi, Hooman, Houtkooper, Riekelt H., Jelier, Rob, Joshi, Chintan, Kothamachu, Varun B., Lewis, Nathan, Lourenço, Artur Bastos, Nie, Yu, Norvaisas, Povilas, Pearce, Juliette, Riccio, Cristian, Rodriguez, Nicolas, Santermans, Toon, Scarcia, Pasquale, Schirra, Horst Joachim, Sheng, Ming, Smith, Reuben, Suriyalaksh, Manusnan, Towbin, Benjamin, Tuli, Mary Ann, van Weeghel, Michel, Weinkove, David, Zečić, Aleksandra, Zimmermann, Johannes, le Novère, Nicolas, Kaleta, Christoph, Witting, Michael & Casanueva, Olivia (2017). WormJam: A consensus C. elegans Metabolic Reconstruction and Metabolomics Community and Workshop Series. Worm 6(2): e1373939.
- Virk, B., Jia, J., Maynard, C.A., Raimundo, A., Lefebvre, J., Richards, S.A., Chetina, N., Liang, Y., Helliwell, N., Cipinska, M. & Weinkove, D. (2016). Folate acts in E. coli to accelerate C. elegans aging independently of bacterial biosynthesis. Cell Reports 14(7): 1611-1620.
- Zhang, C, Yin, A, Li, H, Wang, R, Wu, G, Shen, J, Zhang, M, Wang, L, Hou, Y, Ouyang, H, Zhang, Y, Zheng, Y, Wang, J, Lv, X, Wang, Y, Zhang, F, Zeng, B, Li, W, Yan, F, Zhao, Y, Pang, X, Zhang, X, Fu, H, Chen, F, Zhao, N, Hamaker, BR, Bridgewater, LC, Weinkove, D, Clement, K, Dore, J, Holmes, E, Xiao, H, Zhao, G, Yang, S, Bork, P, Nicholson, JK, Wei, H, Tang, H, Zhang, X & Zhao, L (2015). Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children. EBioMedicine 2(8): 968.
- Weinkove, D. (2013). From aging worms to the influence of the microbiota: an interview with David Weinkove. BMC Biology 11: 94.
- Cabreiro, F., Au, C., Leung, K.-Y., Vergara-Irigaray, N., Cochemé, H.M., Noori, T., Weinkove, D., Schuster, E., Greene, N.D.E. & Gems, D. (2013). Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 153(1): 228-239.
- Virk, B, Correia, G, Dixon, DP, Feyst, I, Jia, J, Oberleitner, N, Briggs, Z, Hodge, E, Edwards, R, Ward, J, Gems, D & Weinkove, D (2012). Excessive folate synthesis limits lifespan in the C. elegans: E. coli aging model. BMC Biology 10: 67.
- Panbianco, C, Weinkove, D, Zanin, E, Jones, D, Divecha, N, Gotta, M & Ahringer, J (2008). A casein kinase 1 and PAR proteins regulate asymmetry of a PIP2 synthesis enzyme for asymmetric spindle positioning. Developmental Cell 15(2): 198-208.
- Weinkove, D, Bastiani, M, Chessa, TAM, Joshi, D, Hauth, L, Cooke, FT, Divecha, N & Schuske, K (2008). Overexpression of PPK-1, the Caenorhabditis elegans Type I PIP kinase, inhibits growth cone collapse in the developing nervous system and causes axonal degeneration in adults. Developmental Biology 313(1): 384-397.
- Bass, TM, Weinkove, D, Houthoofd, K, Gems, D & Partridge, L (2007). Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans. Mechanisms Of Ageing And Development 128(10): 546-552.
- Weinkove, D., Halstead, J.R., Gems, D. & Divecha, N. (2006). Long-term starvation and ageing induce AGE-1/PI 3-kinase-dependent translocation of DAF-16/FOXO to the cytoplasm. BMC Biology 4: 1.
- Jansen, G, Weinkove, D & Plasterk, RHA (2002). The G-protein gamma subunit gpc-1 of the nematode C. elegans is involved in taste adaptation. EMBO Journal 21(5): 986-994.
- Weinkove, D & Leevers, SJ (2000). The genetic control of organ growth: insights from Drosophila. Current Opinion In Genetics & Development 10(1): 75-80.
- Weinkove, D, Neufeld, TP, Twardzik, T, Waterfield, MD & Leevers, SJ (1999). Regulation of imaginal disc cell size, cell number and organ site by Drosophila class I-A phosphoinositide 3-kinase and its adaptor. Current Biology 9(18): 1019-1029.
- Weinkove, D, Poyatos, JA, Greiner, H, Oltra, E, Avalos, J, Fukshansky, L, Barrero, AF & Cerda-Olmedo, E (1998). Mutants of Phycomyces with decreased gallic acid content. Fungal Genetics And Biology 25(3): 196-203.
- Weinkove, D, Leevers, SJ, MacDougall, LK & Waterfield, MD (1997). p60 is an adaptor for the Drosophila phosphoinositide 3-kinase, Dp110. Journal Of Biological Chemistry 272(23): 14606-14610.
- Leevers, SJ, Weinkove, D, MacDougall, LK, Hafen, E & Waterfield, MD (1996). The Drosophila phosphoinositide 3-kinase Dp110 promotes cell growth. EMBO Journal 15(23): 6584-6594.
- Weinkove, D (2015). Model Super-organisms: Can the biochemical genetics of E. coli help us understand aging?. The Biochemist 37(4).
Available for media contact about:
- Biological and Biomedical Sciences: Ageing
- Health & Welfare: Ageing
- Biological and Biomedical Sciences: C. elegans research
- Biological and Biomedical Sciences: Ageing and nutrition in experimental animal models