Cellular metabolism is tightly regulated by many signaling pathways and processes, including lysine acetylation of proteins. While lysine acetylation of metabolic enzymes can directly influence enzyme activity, there is growing evidence that lysine acetylation can also impact protein localization. As the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 has been implicated in a variety of metabolic processes, we have explored whether NuA4 controls the localization and/or protein levels of metabolic proteins. We performed a high-throughput microscopy screen of over 360 GFP-tagged metabolic proteins and identified 23 proteins whose localization and/or abundance changed upon deletion of the NuA4 scaffolding subunit, EAF1. Within this, three proteins were required for glycogen synthesis and 14 proteins were associated with the mitochondria. We determined that in eaf1Δ cells the transcription of glycogen biosynthesis genes is upregulated resulting in increased proteins and glycogen production. Further, in the absence of EAF1, mitochondria are highly fused, increasing in volume approximately 3-fold, and are chaotically distributed but remain functional. Both the increased glycogen synthesis and mitochondrial elongation in eaf1Δ cells are dependent on Bcy1, the yeast regulatory subunit of PKA. Surprisingly, in the absence of EAF1, Bcy1 localization changes from being nuclear to cytoplasmic and PKA activity is altered. We found that NuA4-dependent localization of Bcy1 is dependent on a lysine residue at position 313 of Bcy1. However, the glycogen accumulation and mitochondrial elongation phenotypes of eaf1Δ, while dependent on Bcy1, were not fully dependent on Bcy1-K313 acetylation state and subcellular localization of Bcy1. As NuA4 is highly conserved with the human Tip60 complex, our work may inform human disease biology, revealing new avenues to investigate the role of Tip60 in metabolic diseases.

Graduate students are vital to the creation of research and innovation in Canada. The National Graduate Student Finance Survey was launched in 2021 by the Ottawa Science Policy Network to investigate the financial realities of Canadian graduate students. Closing in April 2022, the survey received 1305 responses from graduate students representing various geographical locations, years of study, fields of education, and demographic backgrounds. The results capture a snapshot into graduate student finances, including an in-depth analysis of stipends, scholarships, debt, tuition, and living expenses. In its entirety, we found that the majority of graduate students are facing serious financial concerns. This is largely due to stagnant funding for students both from federal and provincial granting agencies and from within their institutions. This reality is even worse for international students, members of historically underrepresented communities, and those with dependents, all of whom experience additional challenges that impact their financial security. Based on our findings, we propose several recommendations to the Tri-Council agencies (Natural Sciences and Engineering Research Council, Social Science and Humanities Research Council, and Canadian Institute for Health Research) and academic institutions to strengthen graduate student finances and help sustain the future of research in Canada.

The yeast lysine acetyltransferase, NuA4, is known to be critical important to regulating a variety of cell functions through acetylation of protein targets, resulting in changes in localization, function and/or abundance of its target proteins. Most recently, we have discovered a fascinating role for NuA4 in establishing the balance between lipid droplet formation and phospholipid availability for organelle and cell membranes. This was first discovered upon deletion of the main scaffolding subunit of NuA4 which resulting a strange extension of the nuclear membrane, commonly known as a nuclear flare. This occurs in over 50% of eaf1 cells, compared to only 4% in wild type (WT) cells. Under normal conditions, nuclear flares are primarily detected during mitotic arrest where nuclear membrane production continues unchecked, resulting in excess membrane and nuclear flares. However, nuclear flares in eaf1 cells are detected throughout the cell cycle, suggesting a gross dysregulation of lipid phospholipid production in the absence of NuA4. In addition to nuclear flares, the loss of the NuA4 complex causes significant effects to the vacuole. I have seen experimentally that 60% of all eaf1 cells exhibited severe defects in vacuole fusion, containing more than 10 vacuolar lobes, compared to 7% in WT cells. To further understand this regulation, we set out to find a potential protein target of NuA4‐dependant acetylation that could be the potential link between NuA4 and lipid production. Sitting at the cross‐roads between lipid droplet formation and membrane phospholipid production, phosphatidic acid phosphohydrolase 1 (Pah1) acts as a regulator for lipid biosynthesis in S. cerevisiae. Specifically, Pah1 converts a key metabolite, phosphatidic acid (PA) into diacylglycerol (DAG), which is then subsequently processed to form TAG and stored in lipid droplets. Additionally, it has recently been shown that NuA4 acetylates Pah1, which provides a direct mechanism behind this regulation. We hypothesize that acetylation of Pah1 is required to target the protein to the nuclear and vacuolar membrane. We have seen that upon deletion of EAF1, Pah1 3xGFP has an increase abundance in the cytoplasm and becomes localized to distinct punctate structures in the cell. Suggesting a dramatic change in its localization in the absence of acetylation. Additionally, through use of DAG biosensors, we have seen a drastic movement of DAG pools from the vacuolar membrane to the cytosol and plasma membrane in eaf1 cells. This could explain the defects in vacuole fusion. In its entirety, it has become clear that NuA4 is critical to regulating lipid availability for membranes, and determining the resulting membrane composition. We hope to further characterize the specific relationship between NuA4 and Pah1, in order to determine the how acetylation by NuA4 can affect lipid production for droplets and membranes.

STUDYING CONCUSSIONS WITH A CONCUSSIONany researchers feel an emotional connection to their work, but for Renata Bastos Gottgtroy this takes on a whole new meaning. As a PhD student at Auckland University of Technology in New Zealand, Renata both studies concussions and is afflicted by one.On February 6, 2016, I watched Renata get checked into the boards during an ice hockey game as a member of the York University Lions Women's Hockey Team. As I sat in the stands, suffering from my own concussion, I couldn't help but feel the hit in my bones. Before I knew what was happening, I was running down to the ice. I knew that something was wrong.