A5052090358- Lipid metabolism and biosynthesis
- Photosynthetic Processes and Mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Endoplasmic Reticulum Stress and Disease
- Lipid Membrane Structure and Behavior
- Autophagy in Disease and Therapy
- Pancreatic function and diabetes
- Sphingolipid Metabolism and Signaling
- Fungal and yeast genetics research
- Cell Adhesion Molecules Research
- Organ and Tissue Transplantation Research
- Synthesis of Tetrazole Derivatives
- Nuclear Structure and Function
- Inflammasome and immune disorders
- Platelet Disorders and Treatments
- Plant Molecular Biology Research
- Chemical Thermodynamics and Molecular Structure
- Polysaccharides and Plant Cell Walls
- Synthesis and biological activity
- Research in Cotton Cultivation
- Plant biochemistry and biosynthesis
- Adenosine and Purinergic Signaling
- Immune Response and Inflammation
- Neurological Complications and Syndromes
- Cellular transport and secretion
University of Cambridge
2015-2025
Ave Maria University
2024
UK Dementia Research Institute
2021
Sainsbury Laboratory
2020
Wellcome Trust
2017
Universidade do Porto
2010-2016
Instituto de Biologia Molecular e Celular
2011
Boehringer Ingelheim (United States)
2006
Cell and organelle membranes consist of a complex mixture phospholipids (PLs) that determine their size, shape, function. Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic membranes, yet how cells sense regulate its levels vivo remains unclear. Here we show PCYT1A, rate-limiting enzyme PC synthesis, intranuclear re-locates to nuclear membrane response need for PL synthesis yeast, fly, mammalian cells. By aligning imaging with lipidomic analysis data-driven modeling,...
Perilipins (PLINs) play a key role in energy storage by orchestrating the activity of lipases on surface lipid droplets. Failure this results severe metabolic disease humans. Unlike all other droplet-associated proteins, PLINs localize almost exclusively to phospholipid monolayer surrounding droplet. To understand how they sense and associate with unique topology droplet surface, we studied localization human inSaccharomyces cerevisiae,demonstrating that targeting mechanism is highly...
Partitioning of lipid precursors between membranes and storage is crucial for cell growth, its disruption underlies pathologies such as cancer, obesity, type 2 diabetes. However, the mechanisms signals that regulate this process are largely unknown. In yeast, mainly used phospholipid synthesis in nutrient-rich conditions order to sustain rapid proliferation but redirected triacylglycerol (TAG) stored droplets during starvation. Here we investigate how cells reprogram metabolism endoplasmic...
Abstract Purines are important modulators of bone cell biology. ATP is metabolized into adenosine by human primary osteoblast cells (HPOC); due to very low activity deaminase, the nucleoside end product ecto‐nucleotidase cascade. We, therefore, investigated expression and function receptor subtypes (A 1 , A 2A 2B 3 ) during proliferation osteogenic differentiation HPOC. Adenosine (CPA), (CGS21680C), (NECA), (2‐Cl‐IB‐MECA) agonists concentration‐dependently increased HPOC proliferation....
Lipins are evolutionarily conserved phosphatidate phosphatases that perform key functions in phospholipid, triglyceride, and membrane biogenesis. Translocation of lipins on membranes requires their dephosphorylation by the Nem1p-Spo7p transmembrane phosphatase complex through a poorly understood mechanism. Here we identify carboxy-terminal acidic tail yeast lipin Pah1p as an important regulator this step. Deletion or mutations disrupt binding to translocation. Overexpression drives...
Highlights•Nutrients regulate the phospholipid:diacylglycerol acyltransferase Lro1•Lro1 targets INM subdomain bordering nucleolus•Lro1 is active at and can sustain cell survival during starvation•Compartmentalized synthesis of nuclear TG important for envelope integritySummaryCells dynamically adjust organelle organization in response to growth environmental cues. This requires regulation phospholipids, building blocks membranes, or remodeling their fatty-acyl (FA) composition. FAs are also...
Summary Saccharomyces cerevisiae cells lacking Isc1p, an orthologue of mammalian neutral sphingomyelinase 2, display a shortened lifespan and increased sensitivity to oxidative stress. A lipidomic analysis revealed specific changes in sphingolipids that accompanied the premature ageing Isc1p‐deficient under severe calorie restriction conditions, including decrease dihydrosphingosine levels increase dihydro‐C 26 ‐ceramide phyto‐C levels, latter raising possibility activation...
Abstract Autophagy is a conserved pathway where cytoplasmic contents are engulfed by autophagosomes, which then fuse with lysosomes enabling their degradation. Mutations in core autophagy genes cause neurological conditions, and defects seen neurodegenerative diseases such as Parkinson’s disease Huntington’s disease. Thus, we have sought to understand the cellular perturbations that autophagy-perturbed cells vulnerable seeking negative genetic interactions synthetic lethality autophagy-null...
Sit4p is the catalytic subunit of a ceramide-activated PP2A-like phosphatase that regulates cell cycle, mitochondrial function, oxidative stress resistance and chronological lifespan in yeast. In this study, we show hexokinase 2 (Hxk2p) hyperphosphorylated sit4Δ mutants grown glucose medium by Snf1p-independent mechanism Hxk2p-S15A mutation suppresses phenotypes associated with SIT4 deletion, namely growth arrest at G1 phase, derepression respiration, H2O2 extension. Consistently, activation...
Survival during starvation depends largely on metabolic energy, which is stored in the form of neutral lipids specialized organelles known as lipid droplets. The precursors for synthesis are also used membrane biogenesis, required cell growth and proliferation. Therefore cells must possess mechanisms to preferentially channel toward either or droplet storage, response nutrient status. How this partitioning spatially regulated within endoplasmic reticulum (ER) where droplets co-localize,...
Azole resistant fungal infections remain a health problem for the immune compromised. Current therapies are limited due to rises in new resistance mechanisms. Therefore, it is important identify drug targets discovery and novel therapeutics. Arv1 (are1 are2 required viability 1) function highly conserved between multiple pathogenic species. Candida albicans (C. albicans) cells lacking CaArv1 azole hypersusceptible lack virulence. Saccharomyces cerevisiae (S. cerevisiae) Scarv1 also...
Background:Diacylglycerol kinase produces phosphatidate, a major precursor for the synthesis of membrane phospholipids.Results: The expression diacylglycerol is induced by Reb1p transcription factor, and resulting activity increase essential enzyme function in phospholipid synthesis.Conclusion: Reb1p-mediated transcriptional activation regulates activity.Significance: Diacylglycerol regulated at level transcription.In yeast Saccharomyces cerevisiae, DGK1-encoded catalyzes CTP-dependent...
Triglycerides constitute an inert storage form for fatty acids deposited in lipid droplets and are mobilized to provide metabolic energy or membrane building blocks. The biosynthesis of triglycerides is highly conserved within eukaryotes normally involves the sequential esterification activated with a glycerol backbone. Some eukaryotes, however, can also use cellular lipids as direct acid donors triglyceride synthesis. biological significance pathway that generates at expense organelle...
The synthesis and structural characterization of seven systematically varied aromatic esters are reported. compounds analyzed using single-crystal X-ray diffraction, dynamic scanning calorimetry, variable-temperature viscometry. state the compounds, i.e., liquid solid, is controlled, in part, via sterics ester functionalities which influence presence specific noncovalent interactions solid state. Two distinct conformational polymorphs observed To rationalize formation polymorphs,...
Lupus Nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) that affects kidney function. Here, we investigated the role CD11b, protein encoded by
The biogenesis of membrane-bound organelles involves the synthesis, remodelling and degradation their constituent phospholipids. How these pathways regulate organelle size, remains still poorly understood. Here we demonstrate that a lipid pathway inhibits expansion endoplasmic reticulum (ER) membrane. Phospholipid diacylglycerol acyltransferases (PDATs) use endogenous phospholipids as fatty acyl donors to generate triglyceride stored in droplets. significance this non-canonical biosynthetic...