School of Biosciences

Join us in our journey of discovery


profile image for Dr Campbell Gourlay

Dr Campbell Gourlay

Senior Lecturer in Cell Biology

School of Biosciences

 

Dr Campbell Gourlay joined the school in November 2006. He is a member of the Kent Fungal Group and the Yeast Molecular Biology Group.

Campbell Gourlay began his career at The John Innes Centre in 1996 where he studied the genetic control of leaf development. Following this he began to work with budding yeast as a model eukaryote in the lab of Kathryn Ayscough, where he investigated the role of actin in the process of endocytosis. During this time he discovered a link between actin, the regulation of mitochondrial function and the control of ageing and apoptosis. This led to his involvement in the emerging field of yeast apoptosis, which has popularised the novel concept that unicellular organisms possess the ability to undergo programmed cell death as an altruistic act for the betterment of a population.

In 2006 he was awarded a five year MRC Career Development Fellowship to establish his own lab within the Kent Fungal Group at the University of Kent where is now a lecturer in cell biology. The Gourlay lab maintains a strong interest in the role that actin plays in the control of homeostatic mechanisms that contribute to healthy ageing. Of particular interest are interactions between actin, mitochondria and signal transduction pathways that are crucial to cellular response to stress. The lab also uses yeast as a model eukaryote to study a number of aspects of cancer biology and the toxicity associated with protein aggregations linked to human disease.

back to top

 

Also view these in the Kent Academic Repository
Articles

    Leadsham, Jane E. and Sanders, Geraldine and Giannaki, Samantha et al. (2013) Loss of Cytochrome c Oxidase Promotes RAS-Dependent ROS Production from the ER Resident NADPH Oxidase, Yno1p, in Yeast. Cell Metabolism, 18 (2). pp. 279-286. ISSN 1932-7420.

    Abstract

    Many disease states, including the aging process, are associated with the accumulation of mitochondria harboring respiratory dysfunction. Mitochondrial dysfunction is often accompanied by increased ROS levels that can contribute to cellular dysfunction and disease etiology. Here we use the model eukaryote S. cerevisiae to investigate whether reduced cytochrome c oxidase (COX) activity, commonly reported in aging organisms and associated with neurodegenerative disorders, leads to ROS production from mitochondria. We provide evidence that although reduced COX complex activity correlates with ROS accumulation, mitochondria are not the major production center. Instead we show that COX-deficient mitochondria activate Ras upon their outer membrane that establishes a pro-ROS accumulation environment by suppressing antioxidant defenses and the ERAD-mediated turnover of the ER-localized NADPH oxidase Yno1p. Our data suggest that dysfunctional mitochondria can serve as a signaling platform to promote the loss of redox homeostasis, ROS accumulation, and accelerate aging in yeast.

    Kotiadis, Vassilios N. and Leadsham, Jane E. and Bastow, Emma L. et al. (2012) Identification of new surfaces of cofilin that link mitochondrial function to the control of multi-drug resistance. Journal of Cell Science, 125 (9). pp. 2288-2299. ISSN 0021-9533.

    Abstract

    ADF/cofilin family proteins are essential regulators of actin cytoskeletal dynamics. Recent evidence also implicates cofilin in the regulation of mitochondrial function. Here, we identify new functional surfaces of cofilin that are linked with mitochondrial function and stress responses in the budding yeast Saccharomyces cerevisiae. Our data link surfaces of cofilin that are involved in separable activities of actin filament disassembly or stabilisation, to the regulation of mitochondrial morphology and the activation status of Ras, respectively. Importantly, charge alterations to conserved surfaces of cofilin that do not interfere with its actin regulatory activity lead to a dramatic increase in respiratory function that triggers a retrograde signal to upregulate a battery of ABC transporters and concurrent metabolic changes that support multi-drug resistance. We hypothesise that cofilin functions within a bio-sensing system that connects the cytoskeleton and mitochondrial function to environmental challenge.

    Rinnerthaler, Mark and Buttner, Sabrina and Laun, Peter et al. (2012) Yno1p/Aim14p, a NADPH-oxidase ortholog, controls extramitochondrial reactive oxygen species generation, apoptosis, and actin cable formation in yeast. Proceedings of the National Academy of Sciences, 109 (22). pp. 8658-8663. ISSN 0027-8424.

    Abstract

    The large protein superfamily of NADPH oxidases (NOX enzymes) is found in members of all eukaryotic kingdoms: animals, plants, fungi, and protists. The physiological functions of these NOX enzymes range from defense to specialized oxidative biosynthesis and to signaling. In filamentous fungi, NOX enzymes are involved in signaling cell differentiation, in particular in the formation of fruiting bodies. On the basis of bioinformatics analysis, until now it was believed that the genomes of unicellular fungi like Saccharomyces cerevisiae and Schizosaccharomyces pombe do not harbor genes coding for NOX enzymes. Nevertheless, the genome of S. cerevisiae contains nine ORFs showing sequence similarity to the catalytic subunits of mammalian NOX enzymes, only some of which have been functionally assigned as ferric reductases involved in iron ion transport. Here we show that one of the nine ORFs (YGL160W, AIM14) encodes a genuine NADPH oxidase, which is located in the endoplasmic reticulum (ER) and produces superoxide in a NADPH-dependent fashion. We renamed this ORF YNO1 (yeast NADPH oxidase 1). Overexpression of YNO1 causes YCA1-dependent apoptosis, whereas deletion of the gene makes cells less sensitive to apoptotic stimuli. Several independent lines of evidence point to regulation of the actin cytoskeleton by reactive oxygen species (ROS) produced by Yno1p.

    Jossé, Lyne and Li, Xingmin and Coker, Raymond D. et al. (2011) Transcriptomic and phenotypic analysis of the effects of T-2 toxin on Saccharomyces cerevisiae: evidence of mitochondrial involvement. FEMS Yeast Research, 11 (1). pp. 133-150. ISSN 1567-1356.

    Abstract

    At 5 ?g mL?1, T-2 toxin significantly upregulated the transcription of 281 genes and downregulated 86. Strongly upregulated genes included those involved in redox activity, mitochondrial functions, the response to oxidative stress, and cytoplasmic rRNA transcription and processing. Highly repressed genes have roles in mitochondrial biogenesis, and the expression and stability of cytoplasmic rRNAs. T-2 toxin inhibition of growth was greater in a medium requiring respiration, and was antagonized by antioxidants. T-2 toxin treatment induced reactive oxygen species, caused nucleolytic damage to DNA, probably mitochondrial, and externalization of phosphatidylserine. Deletion mutations causing respiratory deficiency substantially increased toxin tolerance, and deletion of some TOR (target of rapamycin) pathway genes altered T-2 toxin sensitivity. Deletion of FMS1, which plays an indirect role in cytoplasmic protein synthesis, markedly increased toxin tolerance. Overall, the findings suggest that T-2 toxin targets mitochondria, generating oxy-radicals and repressing mitochondrial biogenesis genes, thus inducing oxidative stress and redox enzyme genes, and triggering changes associated with apoptosis. The large transcriptional changes in genes needed for rRNA transcription and expression and the effects of deletion of FMS1 are also consistent with T-2 toxin damage to the cytoplasmic translational mechanism, although it is unclear how this relates to the mitochondrial effects.

    Leadsham, Jane E. and Gourlay, Campbell W. (2010) cAMP/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation. BMC Cell Biology, 11 (92). pp. 1471-2121. ISSN 1471-2121.

    Abstract

    Background Appropriate control of mitochondrial function, morphology and biogenesis are crucial determinants of the general health of eukaryotic cells. It is therefore imperative that we understand the mechanisms that co-ordinate mitochondrial function with environmental signaling systems. The regulation of yeast mitochondrial function in response to nutritional change can be modulated by PKA activity. Unregulated PKA activity can lead to the production of mitochondria that are prone to the production of ROS, and an apoptotic form of cell death. Results We present evidence that mitochondria are sensitive to the level of cAMP/PKA signaling and can respond by modulating levels of respiratory activity or committing to self execution. The inappropriate activation of one of the yeast PKA catalytic subunits, Tpk3p, is sufficient to commit cells to an apoptotic death through transcriptional changes that promote the production of dysfunctional, ROS producing mitochondria. Our data implies that cAMP/PKA regulation of mitochondrial function that promotes apoptosis engages the function of multiple transcription factors, including HAP4, SOK2 and SCO1. Conclusions We propose that in yeast, as is the case in mammalian cells, mitochondrial function and biogenesis are controlled in response to environmental change by the concerted regulation of multiple transcription factors. The visualization of cAMP/TPK3 induced cell death within yeast colonies supports a model that PKA regulation plays a physiological role in coordinating respiratory function and cell death with nutritional status in budding yeast.

    Sudarsha, Sunil and Sourbier, Carole and Kong, Hye-Sik et al. (2009) Fumarate hydratase deficiency in renal cancer induces glycolytic addiction and hypoxia-inducible transcription factor 1 alpha stabilization by glucose-dependent generation of reactive oxygen species. Molecular and Cellular Biology, 29 (15). pp. 4080-4090. ISSN 0270-7306.

    Abstract

    Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an inherited cancer syndrome linked to biallelic inactivation of the gene encoding the tricarboxylic acid cycle enzyme fumarate hydratase (FH). Individuals with HLRCC are at risk to develop cutaneous and uterine leiomyomas and an aggressive form of kidney cancer. Pseudohypoxic drive-the aberrant activation of cellular hypoxia response pathways despite normal oxygen tension-is considered to be a likely mechanism underlying the etiology of this tumor. Pseudohypoxia requires the oxygen-independent stabilization of the alpha subunit of the hypoxia-inducible transcription factor (HIF-1alpha). Under normoxic conditions, proline hydroxylation of HIF-1alpha permits VHL recognition and subsequent targeting for proteasomal degradation. Here, we demonstrate that inactivating mutations of FH in an HLRCC-derived cell line result in glucose-mediated generation of cellular reactive oxygen species (ROS) and ROS-dependent HIF-1alpha stabilization. Additionally, we demonstrate that stable knockdown of FH in immortalized renal epithelial cells results in ROS-dependent HIF-1alpha stabilization. These data reveal that the obligate glycolytic switch present in HLRCC is critical to HIF stabilization via ROS generation.

    Leadsham, Jane E. and Miller, Katherine and Ayscough, Kathryn R. et al. (2009) Whi2p links nutritional sensing to actin-dependent Ras-cAMP-PKA regulation and apoptosis in yeast. Journal of Cell Science, 122 (5). pp. 706-715. ISSN 0021-9533.

    Abstract

    Elucidating the mechanisms by which eukaryotic cells coordinate environmental signals with intracellular ;fate' decisions, such as apoptosis, remains one of the important challenges facing cell biologists. It has recently emerged that the dynamic nature of the actin cytoskeleton is an important factor in the linkage of sensation of extracellular stimuli to signalling mechanisms that regulate programmed cell death. In yeast, actin has been shown to play a role in the regulation of apoptosis as cells prepare themselves for quiescence in the face of nutritional exhaustion, by facilitating the shutdown of Ras-cAMP-PKA pathway activity. Here, we demonstrate that the loss of Whi2p function, a protein known to influence cell cycle exit under conditions of nutritional stress, leads to cell death in yeast that displays the hallmarks of actin-mediated apoptosis. We show that actin-mediated apoptosis occurs as a result of inappropriate Ras-cAMP-PKA activity in Deltawhi2 cells. Cells lacking Whi2p function exhibit an aberrant accumulation of activated Ras2 at the mitochondria in response to nutritional depletion. This study provides evidence that the shutdown of cAMP-PKA signalling activity in wild-type cells involves Whi2p-dependent targeting of Ras2p to the vacuole for proteolysis. We also demonstrate for the first time that Whi2p-dependent regulation of cAMP-PKA signalling plays a physiological role in the differentiation of yeast colonies by facilitating elaboration of distinct zones of cell death.

    Leadsham, Jane E. and Gourlay, Campbell W. (2008) Cytoskeletal induced apoptosis in yeast. Biochimica et biophysica acta Molceular Cell Research, 1783 (7). pp. 1406-1412. ISSN 0167-4889.

    Abstract

    The influence of the cytoskeleton reaches into almost every aspect of eukaryotic cell function. It is a little surprise therefore that links between the regulation of the cytoskeleton and apoptosis have been found in a variety of eukaryotic systems. Studies from yeast have made a significant contribution to this new field of research and have highlighted the importance of interactions between the cytoskeleton and mitochondria in determining cell fate. In yeast both the actin and microtubular cytoskeletons have been shown to influence mitochondrial function and the commitment to apoptosis. In this review we discuss the recent advances and speculate that apoptotic mechanisms that feed off the ability of the cytoskeleton to respond to environmental signals may represent a useful mechanism to remove weak or damaged individuals from a population.

    Franklin-Tong, V.E. and Gourlay, Campbell W. (2008) A role for actin in regulating apoptosis/programmed cell death: evidence spanning yeast, plants and animals. Biochemical Journal, 413 (3). pp. 389-404. ISSN 0264-6021.

    Abstract

    Achieving an understanding of how apoptosis/PCD (programmed cell death) is integrated within cellular responses to environmental and intracellular signals is a daunting task. From the sensation of a stimulus to the point of no return, a programme of cell death must engage specific pro-death components, whose effects can in turn be enhanced or repressed by downstream regulatory factors. In recent years, considerable progress has been made in our understanding of how components involved in these processes function. We now know that some of the factors involved in PCD networks have ancient origins that pre-date multicellularity and, indeed, eukaryotes themselves. A subject attracting much attention is the role that the actin cytoskeleton, itself a cellular component with ancient origins, plays in cell death regulation. Actin, a key cellular component, has an established role as a cellular sensor, with reorganization and alterations in actin dynamics being a well known consequence of signalling. A range of studies have revealed that actin also plays a key role in apoptosis/PCD regulation. Evidence implicating actin as a regulator of eukaryotic cell death has emerged from studies from the Animal, Plant and Fungal Kingdoms. Here we review recent data that provide evidence for an active, functional role for actin in determining whether PCD is triggered and executed, and discuss these findings within the context of regulation of actin dynamics.

    Gourlay, Campbell W. and Ayscough, Kathryn R. (2006) Actin-Induced Hyperactivation of the Ras Signaling Pathway Leads to Apoptosis in Saccharomyces cerevisiae. Molecular and Cellular Biology, 26 (17). pp. 6487-6501.

    Abstract

    Recent research has revealed a conserved role for the actin cytoskeleton in the regulation of aging and apoptosis among eukaryotes. Here we show that the stabilization of the actin cytoskeleton caused by deletion of Sla1p or End3p leads to hyperactivation of the Ras signaling pathway. The consequent rise in cyclic AMP (cAMP) levels leads to the loss of mitochondrial membrane potential, accumulation of reactive oxygen species (ROS), and cell death. We have established a mechanistic link between Ras signaling and actin by demonstrating that ROS production in actin-stabilized cells is dependent on the G-actin binding region of the cyclase-associated protein Srv2p/CAP. Furthermore, the artificial elevation of cAMP directly mimics the apoptotic phenotypes displayed by actin-stabilized cells. The effect of cAMP elevation in inducing actin-mediated apoptosis functions primarily through the Tpk3p subunit of protein kinase A. This pathway represents the first defined link between environmental sensing, actin remodeling, and apoptosis in Saccharomyces cerevisiae.

    Gourlay, Campbell W. and Du, Wei and Ayscough, Kathryn R. (2006) Apoptosis in yeast--mechanisms and benefits to a unicellular organism. Molecular Microbiology, 62 (6). pp. 1515-1521. ISSN 0950-382X.

    Abstract

    Initial observations that the budding yeast Saccharomyces cerevisiae can be induced to undergo a form of cell death exhibiting typical markers of apoptosis has led to the emergence of a thriving new field of research. Since this discovery, a number of conserved pro- and antiapoptotic proteins have been identified in yeast. Indeed, early experiments have successfully validated yeasts as a powerful genetic tool with which to investigate mechanisms of apoptosis. However, we still have little understanding as to why programmes of cell suicide exist in unicellular organisms and how they may be benefit such organisms. Recent research has begun to elucidate pathways that regulate yeast apoptosis in response to environmental stimuli. These reports strengthen the idea that physiologically relevant mechanisms of programmed cell death are present, and that these function as important regulators of yeast cell populations.

    Gourlay, Campbell W. and Ayscough, Kathryn R. (2005) Identification of an upstream regulatory pathway controlling actin-mediated apoptosis in yeast. Journal of Cell Science, 118. pp. 2119-2132. ISSN 0021-9533.

    Abstract

    The build up of reactive oxygen species (ROS) is known to contribute to a reduction in the lifespan of a cell and to their degeneration in diseases such as Alzheimer's and tissue ischaemia. It is therefore important to elucidate pathways that regulate cellular oxidative stress. We have previously shown that actin dynamics can affect the oxidative-stress burden on a yeast cell and thereby its potential lifespan. To elucidate further the connection between actin dynamics and oxidative stress, we sought to identify regulators of this process. The actin regulatory proteins Sla1p and End3p are important in maintaining a rapid turnover of F-actin in cortical patches. We show that cells expressing a mutated form of Sla1p or lacking End3p display markers of apoptosis such as depolarized mitochondrial membranes and elevated levels of reactive oxygen species. Overexpression of the ubiquitin ligase RSP5 can alleviate the oxidative-stress phenotype observed in cells lacking End3p by targeting Sla1p to the cortex and restoring actin remodelling capability. We also demonstrate that overexpression of PDE2, a negative regulator of the Ras/cAMP pathway rescues actin dynamics, reduces oxidative stress sensitivity and restores viability in deltaend3 cells. Our data suggest, for the first time, that a physiological link exists between actin regulation and cAMP signalling that regulates apoptosis in yeast.

    Gourlay, Campbell W. and Ayscough, Kathryn R. (2005) The actin cytoskeleton: a key regulator of apoptosis and ageing? Nature Reviews Molecular Cell Biology, 6 (7). pp. 583-589.

    Abstract

    Evidence from many organisms has shown that the accumulation of reactive oxygen species (ROS) has a detrimental effect on cell well-being. High levels of ROS have been linked to programmed cell death pathways and to ageing. Recent reports have implicated changes to the dynamics of the actin cytoskeleton in the release of ROS from mitochondria and subsequent cell death.

    Gourlay, Campbell W. and Carpp, Lindsay N. and Timpson, Paul et al. (2004) A role for the actin cytoskeleton in cell death and aging in yeast. Journal of Cell Biology, 164 (6). pp. 803-809. ISSN 0021-9525.

    Abstract

    Several determinants of aging, including metabolic capacity and genetic stability, are recognized in both yeast and humans. However, many aspects of the pathways leading to cell death remain to be elucidated. Here we report a role for the actin cytoskeleton both in cell death and in promoting longevity. We have analyzed yeast strains expressing mutants with either increased or decreased actin dynamics. We show that decreased actin dynamics causes depolarization of the mitochondrial membrane and an increase in reactive oxygen species (ROS) production, resulting in cell death. Important, however, is the demonstration that increasing actin dynamics, either by a specific actin allele or by deletion of a gene encoding the actin-bundling protein Scp1p, can increase lifespan by over 65%. Increased longevity appears to be due to these cells producing lower than wild-type levels of ROS. Homology between Scp1p and mammalian SM22/transgelin, which itself has been isolated in senescence screens, suggests a conserved mechanism linking aging to actin stability.

    Gourlay, Campbell W. and Dewar, Hilary and Warren, Derek T. et al. (2003) An interaction between Sla1p and Sla2p plays a role in regulating actin dynamics and endocytosis in budding yeast. Journal of Cell Science, 116 (12). pp. 2551-2564. ISSN 0021-9533.

    Abstract

    The importance of a dynamic actin cytoskeleton for facilitating endocytosis has been recognised for many years in budding yeast and is increasingly recognised in mammalian cells. However, the mechanism for actin recruitment and the role it plays in endocytosis is unclear. Here we show the importance of two yeast proteins in this process. We demonstrate that Sla1p and Sla2p interact in vitro and in vivo and that this interaction is mediated by the central domain of Sla2p, which includes its coiled-coil region, and by a domain of Sla1p between residues 118 and 361. Overexpression of the interacting fragment of Sla1p causes reduced fluid-phase endocytosis and, interestingly, defects in subsequent trafficking to vacuoles. We show that Sla2p is required for the polarised localisation of Sla1p in cells but not for its cortical localisation or for its overlapping localisation with actin. Generation of an Deltasla1Deltasla2 double mutant demonstrates that Sla2p is likely to act upstream of Sla1p in endocytosis, whereas sensitivity to latrunculin-A suggests that the proteins have opposite effects on actin dynamics. We propose that Sla2p recruits Sla1p to endocytic sites. Sla1p and its associated protein Pan1p then regulate actin assembly through interactions with Arp2/3 and Arp2/3-activating proteins Abp1p and Las17/Bee1p.

    Warren, Derek T. and Andrews, Paul D. and Gourlay, Campbell W. et al. (2002) Sla1p couples the yeast endocytic machinery to proteins regulating actin dynamics. Journal of Cell Science, 115 (8). pp. 1703-1715. ISSN 0021-9533.

    Abstract

    Sla1p is a protein required for cortical actin patch structure and organisation in budding yeast. Here we use a combination of immunofluorescence microscopy and biochemical approaches to demonstrate interactions of Sla1p both with proteins regulating actin dynamics and with proteins required for endocytosis. Using Sla1p-binding studies we reveal association of Sla1p with two proteins known to be important for activation of the Arp2/3 complex in yeast, Abp1p and the yeast WASP homologue Las17p/Bee1p. A recent report of Sla1p association with Pan1p puts Sla1p in the currently unique position of being the only yeast protein known to interact with all three known Arp2/3-activating proteins in yeast. Localisation of Sla1p at the cell cortex is, however, dependent on the EH-domain-containing protein End3p, which is part of the yeast endocytic machinery. Using spectral variants of GFP on Sla1p (YFP) and on Abp1p (CFP) we show for the first time that these proteins can exist in discrete complexes at the cell cortex. However, the detection of a significant FRET signal means that these proteins also come close together in a single complex, and it is in this larger complex that we propose that Sla1p binding to Abp1p and Las17p/Bee1p is able to link actin dynamics to the endocytic machinery. Finally, we demonstrate marked defects in both fluid-phase and receptor-mediated endocytosis in cells that do not express SLA1, indicating that Sla1p is central to the requirement in yeast to couple endocytosis with the actin cytoskeleton.

    Dewar, Hilary and Warren, Derek T. and Gardiner, F.C. et al. (2002) Novel proteins linking the actin cytoskeleton to the endocytic machinery in Saccharomyces cerevisiae. Molecular Biology of the Cell, 13 (10). pp. 3646-3661. ISSN 1059-1524.

    Abstract

    The importance of coupling the process of endocytosis to factors regulating actin dynamics has been clearly demonstrated in yeast, and many proteins involved in these mechanisms have been identified and characterized. Here we demonstrate the importance of two additional cortical components, Ysc84p and Lsb5p, which together are essential for the organization of the actin cytoskeleton and for fluid phase endocytosis. Both Ysc84p and Lsb5p were identified through two-hybrid screens with different domains of the adaptor protein Sla1p. Ysc84p colocalizes with cortical actin and requires the presence of an intact actin cytoskeleton for its cortical localization. Ycl034w/Lsb5p localizes to the cell cortex but does not colocalize with actin. The Lsb5 protein contains putative VHS and GAT domains as well as an NPF motif, which are all domains characteristic of proteins involved in membrane trafficking. Deletion of either gene alone does not confer any dramatic phenotype on cells. However, deletion of both genes is lethal at elevated temperatures. Furthermore, at all temperatures this double mutant has depolarized actin and an almost undetectable level of fluid phase endocytosis. Our data demonstrate that Ysc84p and Lsb5p are important components of complexes involved in overlapping pathways coupling endocytosis with the actin cytoskeleton in yeast.

    Hofer, Julie M.I. and Gourlay, Campbell W. and Michael, Anthony et al. (2001) Expression of a class 1 knotted1-like homeobox gene is down-regulated in pea compound leaf primordia. Plant Molecular Biology, 45 (4). pp. 387-398. ISSN 0167-4412.

    Abstract

    Differences in knotted1-like (knox) gene expression may account for some of the diversity of leaf forms seen in nature. Class 1 knox genes are expressed in the compound leaf primordia of tomato but not in the simple leaf primordia of a range of species examined so far. In order to test the hypothesis that all compound leaves differ from simple leaves in this way, we isolated a class 1 knox cDNA from pea, Pskn1 (Pisum sativum knotted1) and examined its expression pattern. The encoded homeodomain of Pskn1 shares 88% identical residues with KNOTTED1 from maize and an adjacent ELK domain is present. The protein sequence of PSKN1 is 69% identical to TKN2, its nearest related sequence in tomato. Unlike TKn2, Pskn1 was not expressed in newly initiated compound leaves. The expression pattern of Pskn1 resembled those of other class 1 knox genes described in maize and Arabidopsis. Transcripts were detected in the shoot apical meristem and developing vasculature of the vegetative shoot, but expression was not detected in newly initiated and developing compound leaf primordia. The same pattern of expression was observed in the afila mutant, which is characterised by highly ramified compound leaves. Our results suggest that tomato and pea use different developmental processes in the generation of their compound leaves.

    Gourlay, Campbell W. and Hofer, Julie M.I. and Ellis, T.H. Noel (2000) Pea compound leaf architecture is regulated by interactions among the genes UNIFOLIATA, cochleata, afila, and tendril-less. Plant Cell. ISSN 1040-4651.

    Abstract

    The compound leaf primordium of pea represents a marginal blastozone that initiates organ primordia, in an acropetal manner, from its growing distal region. The UNIFOLIATA (UNI) gene is important in marginal blastozone maintenance because loss or reduction of its function results in uni mutant leaves of reduced complexity. In this study, we show that UNI is expressed in the leaf blastozone over the period in which organ primordia are initiated and is downregulated at the time of leaf primordium determination. Prolonged UNI expression was associated with increased blastozone activity in the complex leaves of afila (af), cochleata (coch), and afila tendril-less (af tl) mutant plants. Our analysis suggests that UNI expression is negatively regulated by COCH in stipule primordia, by AF in proximal leaflet primordia, and by AF and TL in distal and terminal tendril primordia. We propose that the control of UNI expression by AF, TL, and COCH is important in the regulation of blastozone activity and pattern formation in the compound leaf primordium of the pea.

Conference Items

    Gourlay, Campbell W. and Ayscough, Kathryn R. (2005) A role for actin in aging and apoptosis. In: BioScience 2005 Conference, Jul 17-21, 2005, Glasgow, Scotland.

    Abstract

    The actin cytoskeleton is central to many cell processes including membrane trafficking and generation of cell polarity. We have identified a role for actin in cell death and in promoting longevity of the budding yeast, Saccharomyces cerevisiae. Aging in yeast appears to occur via an apoptotic-like pathway with changes including DNA fragmentation, loss of mitochondrial membrane permeability, increase in levels of ROS (reactive oxygen species) and exposure of phosphatidylserine in the outer leaflet of the plasma membrane. This pathway can be induced by alterations in actin dynamics, such that reduced dynamics correlates with increased levels of ROS and decreased viability. Conversely, increased actin dynamics correlates with low ROS levels and increased survival. Our current studies have focused on identifying pathways which couple changes in actin dynamics to cell death.

    Gourlay, Campbell W. and Ayscough, Kathryn R. (2005) The actin cytoskeleton in ageing and apoptosis. In: 3rd International Meeting on Yeast Apoptosis, Austria, Aug, 2004, Salzburg,.

    Abstract

    Regulated cell death, or apoptosis, has evolved to fulfil a myriad of functions amongst multicellular organisms. It is now apparent that programmed cell death occurs in unicellular organisms such as yeast. In yeast, as in higher eukaryotes, the actin cytoskeleton is an essential component of a number of cellular activities, and many of the regulatory proteins involved are highly conserved. Recent evidence from diverse eukaryotic systems suggests that the actin cytoskeleton has a role in regulating apoptosis via interactions with the mitochondria. This interaction also appears to have a significant impact on the management of oxidative stress and so cellular ageing. In this mini-review we summarise some of the work, which suggests that actin is a key regulator of apoptosis and ageing in eukaryotic cells.

Total publications in KAR: 21 [See all in KAR]

 

back to top

Our main research aim is to utilise the power of the simple model eukaryotic budding yeast to further our knowledge as to how cells function and respond to their environment. As such our current projects and interests span a number of disciplines including:

  1. The regulation of mitochondrial health and production of reactive oxygen species
  2. The role of translational accuracy in healthy ageing and apoptosis
  3. Understanding how mitochondrial function can be harnessed to improve recombinant protein production yields
  4. Roles for the actin cytoskeleton in regulating stress response mechanisms
  5. Developing yeast as a model for motor neuron disease
  6. Using yeast to understand the development of drug resistance

If you are interested in joining the group then please contact:
Dr Campbell Gourlay

back to top

Enquiries: Phone: +44 (0)1227 823743

School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ

Last Updated: 26/09/2014