Laboratory of Molecular Integrative Physiology in Drosophila

Energy distribution in Drosophila Regulation of energy distribution into different organs is crucial for the organism. Immune response requires increased amount of energy/nutrition and overall metabolism adjustment is thus necessary. We are interested in an inter-organ communication which ensures proper energy re-distribution during immune response in Drosophila melanogaster model.You can watch the presentation of our lab on YouTube

 

 

We employ three different types of infection in our experimental models – ① parasitoid wasp Leptopilina boulardi infection of Drosophila larvae, ② extracellular bacteria Streptococcus pneumonia infection of Drosophila adult fly causing an acute infection and ③ intracellular Listeria monocytogenes infection of adult fly causing a chronic infection. We analyze tissue-specific gene expressions and signaling, metabolites, effects on development and behavior throughout the infection course and test impact of various genetic manipulations on observed changes in systemic physiology.

Recently, we found that a systemic metabolic switch, which changes flow of energy from development towards immunity during immune response, is mediated by extracellular adenosine (e-Ado):

Bajgar PLoS Biology 2015 - click to see article

e-Ado is released from immune cells, which are activated to proliferate and differentiate into lamellocytes upon parasitoid wasp attack. Lamellocytes production requires energy, which is obtained by slowing down the host development. The switch from development to immune response requires e-Ado as a mediator. By releasing e-Ado, immune cells are able to usurp energy from the rest of the organism. This experimentally demonstrates a selfish behavior of immune system, which is hierarchically above all the other organs in the organism during immune challenge; theoretical concept of selfish immune system in humans was recently proposed by Dr. Reiner Straub.

Is it possible that adenosine plays similar role during immune response in humnas? You can read editorial Adenosine: a selfish-immunity signal? on this topic.

Extracellular adenosine (e-Ado) is an important regulatory molecule with a low physiological concentration that can rapidly increase during tissue damage, inflammation, ischemia or hypoxia. During hypoxia or cellular metabolic stress, adenosine can be transported by nucleoside transporters to extracellular space from cells where its concentration raises up due to excessive breakdown of ATP. e-Ado then informs the surrounding tissues about the metabolic state of the cells/tissues via adenosine receptors. This can lead to various responses as vasodilation, increase of blood flow and therefore substrate delivery or it can stimulate glycogenolysis, providing energy substrates from stores to overcome stress. Increased e-Ado may also lead to a suppression of metabolic processes in certain tissues to conserve overall energy.

Additional information about e-Ado and details of our previous studies of e-Ado role in flies can be found here.

We now focus on:

  • determining the origin of adenosine within immune cells
  • uncovering downstream effects of extracellular adenosine, i.e. how e-Ado executes its systemic metabolic-switch role
  • what is a difference in regulation of Warburg effect in selfish immune cell (usurping energy) and unselfish developing cell (slowing down when there is not enough energy)
  • relationship between e-Ado and cytokines that also regulate systemic metabolism
  • role of e-Ado in adult immune response/metabolism

Schematic representation of project goals

 

 

In our previous work we also modelled cancer in flies

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