One of the significant, unanswered questions in molecular cell biology is how cells manage the synthesis of the
enormous amount of membranes required for cell cycle progression and proliferation. All cell types, from pro- to
eukaryotes must precisely duplicate all cellular components, including membranes, prior to cytokinesis. However,
the growth- and cell cycle-dependence of membrane synthesis is poorly understood. Recently, we discovered that
yeast triglyceride (TG) breakdown catalyzed by Tgl4 lipase, the functional ortholog of murine adipose TG lipase
ATGL, is cell cycle regulated. Phosphorylation of Tgl4 by cyclin-dependent kinase 1 (Cdc28/Cdk1) activates
lipolysis and contributes to membrane biogenesis early in the cell cycle. Conversely, lack of lipolytic activities
results in delayed membrane formation and cell cycle progression. Our data reveal the first link between TG
lipolysis and cell cycle regulatory kinases, and suggest a general mechanism for coordinating membrane
proliferation with the cell cycle (Kurat et al. 2009). Several questions arise from our work, which I am interested in
pursuing using a combined genomic, genetic and biochemical approach: 1) which lipolysis-derived products are
specifically required to drive ("grease") the cell cycle and 2) what are the lipid-dependent cell cycle checkpoints.
The aim of the proposed project is to understand the molecular mechanisms underlying the interplay between TG
homeostasis and the cell cycle. I will focus on the characterization of components of the cell cycle machinery in
the context of defective TG homeostasis and membrane biogenesis. By using defined cell cycle mutants and high-
throughput and high-content screening procedures I will systematically analyze the lipolytic requirements for
proper cell cycle progression.