Dr Harv Isaacs

Research overview

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Cell-cell signalling plays a critical role in establishing the pattern of the early vertebrate embryo. Fibroblast Growth Factor (FGF) peptide ligands have multiple roles in animal development, including early cell-type specification and patterning of the central nervous system. We use the amphibians Xenopus laevis and Xenopus tropicalis as models for our studies in early development. We have analyzed the function of a number targets of FGF signalling in amphibian development, including the Cdx genes, which code for a family of homeodomain transcription factors with roles in the development of all animals. We collaborate with Professor Peter Holland (Dept of Zoology, Oxford) in studying Cdx regulated pathways and their role in animal evolution. 

The phenotype of an amphibian embryo in which the function of the Cdx family has been blocked.

We have undertaken transcriptomic based approaches aimed at identifying novel targets of FGF signaling and are investigating the role of a number of these targets in early embryonic development. Amongst the identified FGF target genes are lin28a lin28b, which codes for a novel RNA binding proteins, implicated as regulators of human embryonic stem cells properties in culture. Our analysis indicates that  amphibian lin28 genes play important roles in mediating the normal responses to growth factor signalling in early development. Other ongoing projects include collaborations with Dr Paul Genever (York) and Dr Betsy Pownall (York) investigating the role of transcriptional repressors in regulating the expression of FGF target genes in development and stem cells. We also collaborate with Dr Gareth Evans (York) investigating the role of neuronal specific isoforms of the Src proto-oncogene in development and the childhood cancer neuroblastoma.

Whole mount in situ hybridisations on neurula stage Xenopus tropicalis embryos. Left- expression of a neuronal marker (n-tubulin) in differentiating neurons. Right-expression of Gsh2 in the neurogenic region.

Teaching and Scholarship

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Teaching provides me with an opportunity to communicate the excitement and challenges of modern biology to students, at all stages of their time at the University of York. I find it particularly rewarding teaching in areas relevant to my own research, and enjoy contributing to the important process of module design and administration, though being chair of the Biology Programme committee.

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At all levels, I aim to communicate my own enthusiasm for the subject matter. My teaching contributes to a coherent strand of lecture courses in the area of cell and developmental biology, through stage 1, 2 and 3 of York Biology BSc and MBiol programmes. These lecture courses progress from the presentation of the fundamental principles of gene regulation and cell signalling, in stage1 “Cell and Developmental Biology”, through a stage 2, intermediate level “Developmental Biology” module, where the guiding concepts and approaches used in studying development of multicellular organisms are introduced, to detailed analyses of primary research literature in the stage 3 module, “Advanced Topics in Developmental Biology”.

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The small group tutorials are a distinctive feature of teaching in York Biology. Through set reading material and discussion, I aim is to instill a sense of excitement in my own area of expertise of cell, developmental and evolutionary biology. We investigate some key subject areas in modern biology, including evolution of developmental mechanisms, gene regulation, cell signaling and cell differentiation. Tutorials are part of transferable skills teaching at York, with the improvement of essay writing and oral presentation skills, a key aim. In second year tutorials students are exposed to the reading of primary research papers, with the aim of developing comprehension and criticism skills. 

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I supervise both Bsc and MBiol undergraduate projects, and aim to give students a genuine flavour of the research process. Typically, projects in my lab involve students in the learning of a wide range of skills, including bioinformatics, embryo culture and gene expression analyses. My interactions with project students, as they learn and gain confidence in a laboratory environment, are some of my most rewarding experiences as a teacher, and for many students, the research project experience has an important influence on the direction that their careers take after graduation. 

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