Name: Dr Sejeong Lee
Group: Hagan Bayley
Ever since I left high school, I have been conducting research and performing experiments to better understand biological phenomena on a molecular level. I majored in Chemistry during my bachelor’s studies at KAIST (Korea Advanced Institute of Science and Technology). Then, I expanded my knowledge and obtained a master’s degree in Biochemistry from KAIST. I felt motivated to study more about health and disease, so I took a master’s course in Molecular Medicine at Georg-August-Universität in Göttingen, Germany. At medical school I learned about evidence-based medicine, in particular about genes associated with disorders and disease-related misassembly of proteins. My growing interest in proteins led me to pursue graduate study on dynamic behaviours of proteins in the ribosome dynamics group at the Max Planck Institute for Biophysical Chemistry. I specialized in membrane protein targeting pathways. As part of my PhD project I investigated the fate of nascent peptides, encoding membrane proteins, from their emergence from the ribosome until their transfer into the cell membrane. While studying the behavior of nascent peptides, I learned that lipid molecules play a significant role in the function of proteins and that lipid molecules surrounding membrane proteins are therefore an interesting target for future experimental studies. To comprehensively tackle open questions about membrane-protein dynamics, I joined the BBSRC-funded project on ‘protein translocation’ in the departments of Chemistry and Biochemistry at Oxford University. For this project, I am investigating outer membrane porins in collaboration with the Robinson group and the Kleanthous group. As a member of Professor Hagan Bayley’s group, I am studying how protein toxins translocate through a transmembrane pore by means of single channel recording.
My current research focus is on studying the permeability of the Gram-negative bacteria outer membrane (OM). The OM evolved to have a sophisticated barrier playing a critical role in response to environmental stress. The permeability of the OM can be studied by observing various substances (e.g. small molecules and proteins) diffusing through transmembrane pores in the OM. A reduced effectiveness of antibiotic treatments is closely related with a reduced permeability across the OM. Gram-negative bacteria evolve a defensive strategy against antimicrobial substances, resulting in antibiotic resistance. Therefore, studying permeability of the Gram-negative OM will help to understand molecular details behind the antibiotic resistance and to develop strategies to fight against it.
The OM is a highly asymmetric lipid bilayer membrane, with large polysaccharides on the outside. This highly impermeable barrier permits the transport of small molecules such as ions and hydrophilic compounds via passive diffusion through OM membrane proteins, porins. It is an uncommon occurrence for bulky or hydrophobic molecules to enter through porins. But it has been reported that bacterial toxin proteins, colicins, can traverse across the OM through porins. However, we still need to gain a better understanding of the translocation mechanisms. Therefore, to reveal the translocation mechanism at the molecular level, I am studying OM porins and the colicin translocation dynamics using a technique called single channel recording. This approach enables me to follow trajectories of a single colicin molecule across the cell membrane in a directional manner and identify translocation events with transient intermediates, which are extremely difficult to detect with other techniques.
A little bit extra
I enjoy studying tiny microbes and finding explanations on how they have evolved to their present state. I am hoping that the findings obtained in my research activities will be useful for novel antibiotic therapies against bacterial infections. In addition to my research, I enjoy engaging with people who are in different fields. I have been organising small meetings and conferences as a committee member of KSEAUK (Korean Scientists and Engineers Association in UK).