My research has encompassed a wide range of biological
systems, including both bacterial and eukaryotic molecular biology.
My recent work has focused on the Archaea, a group of microbes that lies
intermediate between bacteria and eukaryotes, and includes many organisms
from extreme environments, including hyperthermophiles, which are organisms
that can grow at temperatures near to or above 100°C. As far as we know,
these organisms represent the upper temperature limit for biological systems,
and my main objective is to define the molecular adaptations that allow
their metabolism and genomic replication to proceed at temperatures that
destroy "normal" proteins and denature unprotected DNA in seconds.
There are four main objectives in my laboratory at present: 1)
To use genomic and biochemical methods to determine the components of protein
folding pathways in hyperthermophilic Archaea 2) to use genetic approaches to
characterize protein function and stability in thermophiles and hyperthermophiles
3) to isolate novel thermophiles and hyperthermophiles with novel, hydrogen-producing
metabolic pathways, and 4) to sequence the genomes of thermophiles with novel
phylogenetic and physiological properties.
We are attempting to define mutations that manipulate the protein
chaperoning capacity of heat shock proteins from hyperthermophiles. In addition,
we have cloned several genes that represent key functions in protein stabilization,
namely HSP60, small Heat Shock Protein and prefoldin. Using microarray studies,
we are examining the stress responses of the hyperthermophile, Pyrococcus
Using novel cloning methods, we are examining microbial populations
using a "genome" approach to identification and profiling.