Structure and function of the LetA lipid transport family across bacteria and eukaryotes

PROJECT SUMMARY This K99/R00 application details career development and research plans that have been uniquely tailored to facilitate the transition of the principal investigator, Dr. Cristina Santarossa, to an independent academic position. The K99 research program aims to characterize the cellular function of Escherichia coli LetA, a lipid transporter that is conserved across Gram-negative bacteria and certain eukaryotic parasites. The K99 phase involves a strategic career development plan, overseen by a team of multi-disciplinary mentors and collaborators, that will allow Cristina to gain essential training in microbiology and lipidomics and acquire important career skills such as lab management, mentoring, grant writing, and science communication. The plan also includes clear and actionable steps for identifying and successfully obtaining an independent tenure-track faculty position by the end of the K99 phase. The R00 research program then aims to determine the structure and function of LetA proteins that structurally diverged from E. coli LetA. Core research questions include: How can these structural variants facilitate lipid transport? What substrates may they be transporting? What is their cellular role? To address these questions, Cristina has developed a comprehensive research plan that involves identifying the cellular substrates of E. coli LetA and two structural variants from K. pneumoniae and P. falciparum, and structural determination of the LetA structural variants and cellular assays to probe their function. This research will provide key insights into the physiological role of a new mechanism of lipid transport that is likely conserved. The proposed studies will largely take place at Johns Hopkins University, which is home to a vibrant and collegial community of microbiologists, cell biologists, and biophysicists. This environment is ideal to facilitate the successful completion of Cristina’s K99 research program and Cristina’s goal of transitioning to a successful career in independent academic research.