Metallosphaera sedula is the first extremely thermoacidophilic bioleacher to have its complete genome sequenced. Using the sequence, physiological features of importance to biomining can be studied via transcriptional analyses. To this end, a whole genome oligonucleotide microarray has been constructed for M. sedula. Culturing methodologies have been developed to ensure extraction of M. sedula mRNA representing bioleaching conditions, utilizing epifluorescent cell counts and an o-phenanthroline colorimetric assay. Initial results indicate that optimum mRNA sampling time for M. sedula occurs after the third media replacement and an additional 160 hours of growth. Additionally, preliminary efforts have been made to develop a better defined heterotrophic medium for comparison against autotrophic media containing metal sulfide substrates. Finally, evidence that transcriptional response experiments can be carried out successfully in spite of the extreme cultivation conditions is presented.