Grant: Discovery Grants Program - Individual

Nature of the Work My research program aims to investigate the extreme stability and unique properties of archaea Surface layer (S-layer) components for the ultimate purpose to engineer nano-devices in a variety of biotechnological fields. Thereby, we combine Basic -and Applied Science with Bio-engineering and Synthetic Biology. We focus our attention on the structure-property relationship of the unique S-layer protein assembly from Staphylothermus marinus (S. marinus), an extremophilic archaea isolated from deep sea black smoker vents. S. marinus is a strict anaerobic sulfur reducing archaeon that grows at temperatures up to 98°C and has a proteinaceous S-layer consisting of elongated Tetrabrachion units arranged in a 3D-network, called STABLE. As a consequence of its adaptation to the extreme conditions, the S-layer proteins of S. marinus are characterized by an unusual stability. The proposed research will focus on investigating structural and mechanistic features of (i) the 3D-assembly mechanism of Tetrabrachion to form a quasi-crystalline S-layer, (ii) the molecular mechanisms of complex formation between Tetrabrachion and STABLE and (iii) the extreme stability of S-layer components as a foundation for bio-engineering and synthetic biology. A combination of structural, biophysical and synthetic approaches will be performed and offers undergraduate and graduate students a great variety of different skills in modern integrated research programs. Importance Since their discovery, hyperthermophilic archaea have been under intense scrutiny due to their unique adaptations to the extreme environments in which they thrive. However, very little about their 3D structures is known. It is suggested that life has extreme origins, and thus the study of these organisms provides insight into the biology of early life forms. In addition, understanding the molecular mechanisms of their adaptation to the extreme conditions (pH, Temperature, pressure, salinity, ionic strength) makes these microorganisms a perfect research tool for biotechnological developments. Outcome and Benefit The expected outcome for this 5-year program is to obtain mechanistic and chemical information about the extreme stability of archaeal protein assemblies. Here, we aim to understand the molecular basis of their unique adaptation to extreme conditions, that will open new perspectives on our understanding of the origin of life and will provide new insights into development of biotechnological applications in the broad fields of monitoring, remediation and catalytic nano-devices. Over the next 5 years, it is expected that 3-4 graduate students will be engaged in this research program at any given time. Our findings will guide the design and analysis of artificial S-layer assemblies with great impact on Canada's biotech sector. In the long-term, understanding extremophilic adaptations on the molecular level, will provide a molecular fingerprint for advanced nano-device development.