Researchers in the Developmental and Cellular Genetics grouping are employing a range of genetical techniques to study the function of genes within cells of various experimental systems. These include microorganisms such as fungi and parasites, through to multicellular plants and animals. Research areas include: understanding how genes control the ability of fungal pathogens to switch between different growth forms or undergo differentiation to produce asexual spores; understanding how differences in human gene variants can alter susceptibility to malaria parasite infection, and how parasites can sense their environment to modulate density; how plant growth and development are controlled by key gene regulatory complexes; how expression of metastasis genes in the fly can drive cells to detach from their neighbours and become migratory; and how genes encoding metabolic enzymes allow insects to detoxify exogenous chemicals and humans to maintain metal homeostasis.
Labs / Groups
Research Labs and Groups associated with Developmental and Cellular Genetics include:
- Dr Michael Murray – Developmental genetics of Drosophila
Lab head: Dr Michael Murray (contact)
The Murray lab investigates the cellular mechanisms of morphogenesis, which play a central role in the formation of multicellular organisms. One of the most important mechanisms is the ability of cells to switch between a stationary form to a migratory form, and back again. These processes are called the epithelial mesenchymal transition (EMT) and mesenchymal epithelial transition (MET). They are employed at multiple stages during development, but also play a key role in cancer, by allowing cells of a primary tumour to become migratory and metastasise to second sites in the body.
The lab uses the sophisticated genetic tools of the fruit fly Drosophila melanogaster, one of the premier model organisms for biomedical research. In a recent large scale RNAi screen for genes promoting EMT we identified the axonal chemoattractant Netrin. Netrin is required for the 'eversion' of the fly wings, a process involving EMT. Surprisingly, Netrin and its receptor Frazzled/DCC are also required for MET during the formation of the embryonic intestinal epithelium. Using a range of molecular biology techniques and fly genetics we are now unravelling the complex biology of Netrin signalling in controlling EMT and MET. We are also following up on other genes uncovered in the screen, such as the Polycomb Group epigenetic repressors.
- The role of Netrin in the wing eversion EMT;
- The role of Netrin in the MET of the embryonic intestinal epithelium;
- The role of Polycomb Group genes in promoting epithelial/mesenchymal plasticity;
- Prof. Phil Batterham – Neurogenetics, Behaviour and Systems Biology in Insects
Lab head: Professor Phil Batterham (contact)
Our group studies the interaction of chemical insecticides with pest and beneficial insects. Understanding this interaction will underpin the development of more effective and sustainable control strategies, with a reduced environmental impact.
Our research focuses on two widely used classes of insecticides (the neonicotinoids and the spinosyns), both of which target nicotinic acetylcholine receptors (nAChRs) in the insect brain. These insecticides serve as excellent chemical probes that, when used in combination with nAChR customised mutants generated with CRISPR, allow a detailed analysis of the role of specific receptor subunits and neurons in behaviours including mating, locomotion and sleep.
Insecticides, like other toxins, are metabolised and transported around the body. Working with Richard O’Hair’s group in Bio21, we have developed mass spectrometry methods that allow insecticides and their metabolites to be tracked on their journey from ingestion to the brain to excretion. Combining the tools of genetics, toxicology and mass spectrometry, the genes responsible are being identified.
Mutations in the nAChR, metabolic and transporter genes can confer insecticide resistance. In studying these genes in model non-pest insect (the vinegar fly), we have developed the capacity to predict the genetic basis of insecticide resistance before it arises in pests. Thus, our research can improve resistance management strategies for current generation insecticides and improve the design of insecticides of the future.
One of the challenges in working on insect pests has been the lack of available genetic resources to facilitate research. Our laboratory has played a leadership role in the sequencing of the genomes of two major agricultural pests - the sheep blowfly and the cotton bollworm.
- The role of the nAChR subunits in specific behaviours and responses to insecticides
- Identification of genes involved in the transport and metabolism of insecticides
- Impact of sub-lethal doses of insecticide on insect development and behaviour
- Pest insect genomics
- Dr John Golz – Developmental Genetics of the model plant Arabidopsis
Lab head: Dr John Golz (contact)
Work in the Golz group is centred on how complex patterns of gene expression are generated and maintained during cell-type specification and differentiation in multicellular organisms. This problem is being addressed in the model plant Arabidopsis through the analysis of a small group of transcriptional regulators that control cell differentiation in embryos, leaves and the outer layer of the seed coat. The group is also interested in understanding how these transcriptional regulators link developmental responses to environmental stimuli, such as heat and salt stress, as this knowledge underpins efforts to breed crops that can withstand the effects of climate change.
The group is also translating knowledge of developmental regulation to improving the efficiency of genetic transformation in select crop species. The application of this technology will significantly reduce the cost of developing new crop varieties and help the agricultural industry more quickly assess the impact of certain genes on important agricultural traits such as disease resistance.
Work in the Golz group mainly focuses on LEUNIG (LUG) and LEUNIG_HOMOLOG (LUH), two closely related proteins with extensive structural similarity to the transcriptional co-repressor found in yeast, Drosophila and mammals. Neither LUG nor LUH are capable of binding DNA directly, and must therefore interact with DNA binding co-factors (transcription factors; TF) if they are to be recruited to the regulatory sequences of target genes. Some of these interactions are direct, whereas others are indirect and occur via the adaptor proteins SEUSS (SEU) or SEU-LIKE (SLK1-3). As a result of these interactions, LUG/LUH are part of a large regulatory complex.
The group has shown that the LUG regulatory complex diverse processes in the plant including stem cell formation required for sustained plant growth, cell fate acquisition in developing organs, and pectin modification in the developing seed coat. Given the importance of these co-repressors in developmental regulation, the group is continuing to characterize their function.
- Defining and characterizing transcription factors that are part of the LUG regulatory complex
- Identifying the network of regulatory pathways controlled by LUG/LUH and SEU/SLK during embryonic and post-embryonic development
- Investigating the role of the LUG regulatory complex in stress response pathways
- Developing novel approaches to improve the efficiency of genetic transformation in Brassica crops
- A/Prof. Alex Andrianopoulos
Lab head: Associate Professor Alex Andrianopoulos (contact)
- Dr Patricia Jusuf – Visual neuroscience
Lab head: Dr Patricia Jusuf (contact)
Our group is interested in understanding the genetic networks that co-ordinate the generation of different types of neurons in the central nervous system of vertebrates. We use zebrafish as a model and focus on neural specification in the retina in the eye, which has a relatively simpler organisation compared to other CNS regions.
- Prof. Jim Camakaris
Lab head: Professor Jim Camakaris (contact)
- Dr Mike Haydon – Plant cell signaling
Lab head: Dr Mike Haydon (contact)
Once a seed germinates, a plant is restricted to grow in that position for its life cycle. This exposes the plant to a range of predictable and unpredictable changes in its growth environment. For example, it is exposed to daily fluctuations in light availability and temperature, as well as shifts in availability of water and nutrients. Plants can also respond to unpredictable environmental events, such as extremes in temperature. To deal with this, plants must make ‘decisions' at key development stages, such as germination and flowering time, and optimise physiology to cope with rapid changes in conditions. Thus, plants have evolved signalling mechanisms to sense and respond to their environment. In the Haydon lab, our main interests are in energy signalling, cell wall signalling and the circadian clock, and how these impact on plant physiology and development. In particular, we are interested in the interactions between distinct environmental cues such as light and nutrient availability. We use genetics, chemical genetics, molecular biology and biochemistry to decipher the signalling pathways underpinning some of these adaptive mechanisms.
- Genetic and chemical genetic investigation of interactions between sugar and light signalling.
- Roles for signalling from the plant cell wall in photomorphogenesis
- Impact of nutrient status on the circadian network
- Cell-type specific signatures in sugar signalling and the circadian clock