Methane (CH4) is a potent greenhouse gas produced in diverse terrestrial subsurface and marine ecosystems. However, the amount of CH4 emitted to the atmosphere from these ecosystems is largely reduced by methanotrophic microorganisms –microbes that oxidize CH4 to obtain energy and carbon source for their metabolism. Methane oxidation can occur aerobically or anaerobically. While extensive information is available on aerobic methanotrophs’ biochemistry, physiology and ecology, little is known about anaerobic methanotrophs.Anaerobic CH4 oxidation has thus far mostly been investigated in marine ecosystems. There, CH4 oxidation is coupled to the reduction of sulfate. It is believed that the reaction occurs via a syntrophic cooperation in which anaerobic methanotrophs transfer electrons to a sulfate reducing bacterium thus the overall reaction is energetically feasible. However, the exact nature of the syntrophy and the identity of the electron transfer compound(s) remain unknown. Moreover, no pure culture or defined consortium of these microorganisms is available. This hampers detailed metabolic and physiology understanding of the process.Here we propose using innovative bubble-less membrane and electrochemical bioreactors to obtain robust enrichment cultures and to explore the mechanism of electron transfer. The nature of the syntrophy of the microorganisms involved will be assessed using stable isotopes labeled substrates. Incorporation of labeled atoms into biomass –lipids and –fatty acids (LFA) will be determined after cell-sorting of fluorescent labeled various archaea, and bacteria cells types. This new approach may allow exploiting the high sensitivity of stable isotope probing of LFA while attaining good microorganisms’ identity resolution. Metabolomic studies of anaerobic CH4 oxidation will be conducted using in vivo 13C-NMR. The results should result in novel strategies to isolate these not yet isolated key players in the global CH4 cycle.