Research Interests
Background (General)
Every living thing renews itself by a process of cell division. In order to produce two new identical cells from one existing cell, the genetic material, the chromosomes, must first be replicated and the volume of the cell must increase. During the process defined as cell division itself, these duplicated chromosomes align in the centre of the cell before one copy of each chromosome is moved to opposite sides of the cell. Finally, the cell physically cleaves in two, usually at the centre of the cell, producing two daughter cells, each identical to themselves and to the original cell.
All cells use protein fibres termed microtubules (MTs) order to faithfully divide. These fibres are made up of repeating units of a protein called tubulin that can be added or taken away from the ends of existing MTs, allowing them to grow and shrink. Other proteins in the cell, called MT associated proteins (MAPs) are able to alter the properties of the MTs, causing them to grow or shrink more quickly, to link existing MTs to each other, or to link the ends of the MTs to chromosomes or other structures in the cell. In this way, MTs can be organised into dynamic structures, capable of doing different things. During cell division, two main MT structures are important - the spindle apparatus, which makes sure the chromosomes line up and are moved apart correctly, and the central spindle, that allows the cell to cleave precisely in two.
Background (Technical)
Cell division is orchestrated by a microtubule (MT) based structure called the spindle apparatus. In most animal cells, the formation of the spindle apparatus is mediated by complex interactions between MTs nucleated by the centrosome, those organised by mitotic DNA, and those seeded by the growing spindle itself. These populations of MTs are organised by a multitude of MT associated proteins (MAPs), including protein motor complexes, to form a polarized and focused spindle capable of chromosome segregation. Following movement of sister chromatids to the spindle poles in anaphase, a bundle of MTs form between the separating DNA. This central spindle assists in the formation of the contractile ring, a transient actin and myosin-II based structure, which is then able to direct cytokinesis.
Aim of the lab
We want to understand how the spindle apparatus and central spindle are organised, and what governs the similarities and differences between these structures in different types of cell. In order to learn as much as possible about this process, we use a combination of quantitative analytical methods and qualitative, descriptive biology.
Why fruit flies?
Drosophila melanogaster has proved to be an excellent system both for studying cell division, and for the isolation of proteins that function during mitosis. There are a number of other labs throughout the world working on distinct aspects of cell division in this model organism. It is a close-knit community of scholars who are open and enthusiastic about advancing the field as quickly as possible.
Other research interests
Obviously, I look to oversee the research being undertaken in the lab in general. In addition, I am interested in the relationship between different scientific approaches, and the way in which they can be combined to provide advances in our understanding of biological processes. The move towards quantitative techniques, driven by technological advances in physical science methods, coupled to the wealth of information accumulated within biology using high-throughput approaches, is now allowing us to measure and analyse sub-cellular processes with a degree of accuracy not previously possible. This provides the researcher with “real” data, which can be combined with statistical methods and powerful computational tools to build models of biological processes that can be tested. However, I believe it is important to view such analyses within the context of the biological process being studied. Humans are able to process visual information and relate it to their previous experiences and accumulated knowledge in a manner impossible for computers. Immersing oneself in the viewing experience can lead to a greater understanding of the way in which a biological process ‘works‘. Such experiential, intuitive biology has been practiced for centuries and has led to many of the great advances in biology, medicine and related disciplines. By combining the recently advanced quantitative techniques and historically valuable qualitative approaches, I believe science will be able to move towards its goal of understanding the world in which we live more quickly than using one approach alone.
Research projects
1. Identification and characterisation of novel MAPs with roles in cell division
2. Understanding the way in which the Augmin complex works to supplement microtubule nucleation from within the mitotic spindle
3. Understanding the role of the chromosomal passenger complex (CPC) in central spindle assembly and cytokinesis
4. Automated quantitative analysis of microtubule and chromosome dynamics
Research networks
Hiro Ohkura, University of Edinburgh, UK
David Sharp, Einstein College of Medicine, NY, USA
Maria Grazia Giansanti, Universita di Roma ‘La Sapienza‘, Italy
Charlotte Deane, Department of Statistics, University of Oxford, UK
Alison Noble, Department of Engineering, University of Oxford, UK
Every living thing renews itself by a process of cell division. In order to produce two new identical cells from one existing cell, the genetic material, the chromosomes, must first be replicated and the volume of the cell must increase. During the process defined as cell division itself, these duplicated chromosomes align in the centre of the cell before one copy of each chromosome is moved to opposite sides of the cell. Finally, the cell physically cleaves in two, usually at the centre of the cell, producing two daughter cells, each identical to themselves and to the original cell.
All cells use protein fibres termed microtubules (MTs) order to faithfully divide. These fibres are made up of repeating units of a protein called tubulin that can be added or taken away from the ends of existing MTs, allowing them to grow and shrink. Other proteins in the cell, called MT associated proteins (MAPs) are able to alter the properties of the MTs, causing them to grow or shrink more quickly, to link existing MTs to each other, or to link the ends of the MTs to chromosomes or other structures in the cell. In this way, MTs can be organised into dynamic structures, capable of doing different things. During cell division, two main MT structures are important - the spindle apparatus, which makes sure the chromosomes line up and are moved apart correctly, and the central spindle, that allows the cell to cleave precisely in two.
Background (Technical)
Cell division is orchestrated by a microtubule (MT) based structure called the spindle apparatus. In most animal cells, the formation of the spindle apparatus is mediated by complex interactions between MTs nucleated by the centrosome, those organised by mitotic DNA, and those seeded by the growing spindle itself. These populations of MTs are organised by a multitude of MT associated proteins (MAPs), including protein motor complexes, to form a polarized and focused spindle capable of chromosome segregation. Following movement of sister chromatids to the spindle poles in anaphase, a bundle of MTs form between the separating DNA. This central spindle assists in the formation of the contractile ring, a transient actin and myosin-II based structure, which is then able to direct cytokinesis.
Aim of the lab
We want to understand how the spindle apparatus and central spindle are organised, and what governs the similarities and differences between these structures in different types of cell. In order to learn as much as possible about this process, we use a combination of quantitative analytical methods and qualitative, descriptive biology.
Why fruit flies?
Drosophila melanogaster has proved to be an excellent system both for studying cell division, and for the isolation of proteins that function during mitosis. There are a number of other labs throughout the world working on distinct aspects of cell division in this model organism. It is a close-knit community of scholars who are open and enthusiastic about advancing the field as quickly as possible.
Other research interests
Obviously, I look to oversee the research being undertaken in the lab in general. In addition, I am interested in the relationship between different scientific approaches, and the way in which they can be combined to provide advances in our understanding of biological processes. The move towards quantitative techniques, driven by technological advances in physical science methods, coupled to the wealth of information accumulated within biology using high-throughput approaches, is now allowing us to measure and analyse sub-cellular processes with a degree of accuracy not previously possible. This provides the researcher with “real” data, which can be combined with statistical methods and powerful computational tools to build models of biological processes that can be tested. However, I believe it is important to view such analyses within the context of the biological process being studied. Humans are able to process visual information and relate it to their previous experiences and accumulated knowledge in a manner impossible for computers. Immersing oneself in the viewing experience can lead to a greater understanding of the way in which a biological process ‘works‘. Such experiential, intuitive biology has been practiced for centuries and has led to many of the great advances in biology, medicine and related disciplines. By combining the recently advanced quantitative techniques and historically valuable qualitative approaches, I believe science will be able to move towards its goal of understanding the world in which we live more quickly than using one approach alone.
Research projects
1. Identification and characterisation of novel MAPs with roles in cell division
2. Understanding the way in which the Augmin complex works to supplement microtubule nucleation from within the mitotic spindle
3. Understanding the role of the chromosomal passenger complex (CPC) in central spindle assembly and cytokinesis
4. Automated quantitative analysis of microtubule and chromosome dynamics
Research networks
Hiro Ohkura, University of Edinburgh, UK
David Sharp, Einstein College of Medicine, NY, USA
Maria Grazia Giansanti, Universita di Roma ‘La Sapienza‘, Italy
Charlotte Deane, Department of Statistics, University of Oxford, UK
Alison Noble, Department of Engineering, University of Oxford, UK
