Isopentenyl pyrophosphate (IPP) is the main building block for synthesis of various isoprenoid compounds that are essential for cell survival, such as cholesterol, vitamins and hormones. Two pathways exist for synthesizing IPP, 1) in some bacteria, fungi, archaea and eukaryotes the mevalonate (MVA) pathway is used.  2) Most bacteria and apicomplexan parasites, like malaria and toxoplasma use the methylene erythriol phosphate (MEP) pathway, which includes an important IPP-precursor, E-4-hydroxy-3methyl-but-2-enyl pyrophosphate (HMBPP). Plants and a few bacteria use both the MEP and MVA pathways. Both IPP and HMBPP act as nonpeptide pattern molecules (PAMPs) but are also designated phosphoantigens (pAg). These are intensively studied in pathogens like Tuberculosis bacilli and Plasmodium falciparum and in cancer. IPP only differs from HMBPP by a hydroxyl group. However, more than 10,000 times higher concentrations are required of IPP to reach an effect equivalent of HMBPP on the proliferation and activation of Vγ2Vδ9 T cell. This may be since IPP is also made in humans and only at the high levels caused by tumors it will cause a cellular defense reaction.

The balance between MEP/MVA bacteria in human gut microbiota has not been studied before and our present aim is to investigate this. A distorted gut flora is known to contribute to several disease conditions like, obesity, anorexia, mental illness etc.  
In a pilot study, we fed mice by oral gavage with a low dose of HMBPP, IPP or water and the weight gain was recorded. In addition, we followed gene transcription in brain, gut, and small intestine. In a next set the transcriptome of liver, spleen, kidney and salivary glands is analyzed for immune gene upregulation.
We then use MEP or MVA pathway inhibitors to treat feces from healthy humans.  From the samples achieved, bacteria are determined by 16S RNA sequencing to confirm the MEP or MVA bacterial content. Germ free (GF) mice are treated by oral gavage with mainly MEP or MVA pathway microbiota and their effects on behavior, appetite and transcription in different mice tissues are followed. 
 
We welcome Master students for 30-60hp (1/2-1 year) research projects. A theoretical and a practical course on experimental animal work may be included in these projects.

Selected publications

Liu, Chenxiao; Emami, S. Noushin; Pettersson, Jean; Faye, Ingrid; Ranford–Cartwright, Lisa; Parmryd, Ingela.
V gamma 9V delta 2 T cells proliferate in response to phosphoantigens released from erythrocytes infected with asexual and gametocyte stage Plasmodium falciparum
Cellular Immunology, 2018 1090-2163, Vol. 334, s. 11-19

Emami, S. Noushin; Lindberg, Bo G.; Hua, Susanna; Hill, Sharon; Mozuraitis, Raimondas; Lehmann, Philipp; Birgersson, Göran; Borg-Karlson, Anna-Karin; Ignell, Rickard; Faye, Ingrid.
A key malaria metabolite modulates vector blood seeking, feeding, and susceptibility to infection. Science. 2017 Feb, DOI: 10.1126/science.aah4563

Kukutla. P.; Lindberg. BG.; Pei. D., Rayl. M.; Yu. W., Steritz. M.; Faye. I.; Xu. J.
Insights from the genome annotation of Elizabethkingia anophelis from the malaria vector Anopheles gambiae. PLoS One. 2014 May 19;9(5)

Lindberg. BG.; Merritt. EA.; Rayl. M, Liu. C.; Parmryd. I.; Olofsson. B.; Faye. I. 
Immunogenic and antioxidant effects of a pathogen-associated prenyl pyrophosphate in Anopheles gambiae. PLoS One. 2013 Aug 13;8(8)