Molecular Regulation of Epigenetic Inheritance of Metabolic Disease

One can be programmed to be fat?

New evidence suggests that metabolic memories, set by the parents, can affect eating behavior and obesity in future generations. The concept of us inheriting more then the genes from our parents’, and that this inheritance is dependent on environmental cues, touches on the theories of “soft inheritance” and “use and disuse inheritance” suggested by Lamarck and Darwin. 

Foto: Thor BalkhedThe molecular mechanisms behind this transfer of environmental information over generations is still largely unknown and are at the moment under intense investigation.

Humans as well

We recently published a model of paternal diet-induced obesity in Drosophila. Similar to findings in mammals, we found that both low and high-sugar diets in Drosophila adult males elicit obesity in the next generation. Capitalizing on the large number of genetic tools available in Drosophila we could show that paternal high-sugar diet reprograms select chromatin in the offspring. Most importantly, we found similar changes in chromatin structure to be associated with human obesity. 

By using this model, in combination with the extensive genetic tool-box of Drosophila melanogaster and state of the art techniques such as next generation sequencing, iCLIP and CLASH, we now aim to define the carrier of environmental information in sperm and the early molecular event in embryogenesis underlying metabolic memories.

Fig 1. Photographer: Adeleheid Lempradl

Paternal sugar alters offspring epigenetic signatures.

Fig 1. One elegant method to examine modulation of repressed chromatin states in vivo in Drosophila is Position-effect-variegation (PEV). PEV exploits insertion site dependent silencing of a pigment-enabling white allele as a simple and robust reporter for heterochromatin silencing.

We have tested 8 different PEV strains and found one, wm4h, which reports paternal intergenerational metabolic response (IGMR) (Figure1). Intriguingly, the eye color of wm4h F1 flies correlates closely with their triglyceride stores, pointing out this position-effect-variegation strain to be an excellent reporter for paternally induced metabolic phenotypes.

Forskare inom epigenetik

Open Positions
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Postdoc positions

Two funded postdoc positions are available for researchers with a proven track record in small RNA sequencing, ChIPseq, CLASH and/or iCLIP, preferably using Drosophila.

Master thesis

We welcome outstanding students with an interest in epigenetics and inter/transgenerational inheritance. You should have an experimental biology background such as medical biology or equivalent.

To apply

Send me your CV, one or two references and a short description of your research interest.

Principal investigator
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Publications
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2019

Daniel Nätt, Unn Örtegren Kugelberg, Eduard Casas, Elizabeth Nedstrand, Stefan Zalavary, Pontus Henriksson, Carola Nijm, Julia Jaderquist, Johanna Sandborg, Eva Flinke Carlsson, Rashmi Ramesh, Lovisa Örkenby, Filip Appelkvist, Thomas Lingg, Nicola Guzzi, Cristian Bellodi, Marie Löf, Tanya Vavouri, Anita Öst (2019) Human sperm displays rapid responses to diet PLoS biology , Vol. 17 Continue to DOI

2015

2014

Organisation
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