Dr Dieter Riethmacher BSc., MSc., PhD, Habilitation
Associate Professor in Human Genetics
Dr Dieter Riethmacher is Associate Professor in Human Genetics within Medicine at the University of Southampton.
Dieter was appointed as a Reader in Human Genetics in 2007. Dieter has studied biology in Cologne and completed his Diploma thesis about expression and characterisation of c- and v-mos oncogenes in 1991. He then did his PhD in the Max-Delbrück Laboratory in Cologne working on the molecular regulation of adhesion and proliferation in epithelia using mouse models and cell biology. After completion in 1994 he moved to the Max-Delbrück-Center in Berlin where he continued to work with mouse models to analyse gene function.
In 1999 Dieter was appointed as an independent group leader in the Centre for Molecular Neurobiology in Hamburg. During this time he initially focussed on glial development. He then developed a universal mouse model enabling to analyse cellular functions in complex organs or circuits. He also habilitated in Neurobiology in 2005 at the Faculty of Medicine, University of Hamburg.
Currently Dieter leads a group that is interested in the analysis of cellular function in development, regeneration and disease. His lab is located in the Duthie Building on the Faculty of Medicine Campus.
Dieter has several fruitful collaborations locally and abroad involving mouse models to analyse development and disease.
Qualifications
Diploma, Biology, University of Cologne (Germany), 1991 PhD, Biology, University of Cologne (Germany), 1994 Habilitation, University of Hamburg, 2005
Appointments held
Research Associate, Max-Delbrück Laboratory, Max Planck Institute, Cologne, Gemany, 1994-1995
Senior Research Fellow, Max-Delbrück Centre, Berlin, Germany 1995-1999
Group Leader, Center for Molecular Neurobiology, University of Hamburg, Germany 1999-2007
Reader in Human Genetics, University of Southampton. 2007-present
Research
Responsibilities
Publications
Teaching
Contact
Research interests
GCIP in tumour development
GCIP is involved in cell cycle progression and is localized on the human chromosome 15q15, a locus harbouring a tumour suppressor gene. Our knock-out model enables us to analyse the postulated modulatory role of GCIP during cell cycle progression and also to unravel its role for tumour formation and progression.
Molecules in peripheral nerve regeneration
Taking advantage of a recently developed femoral nerve injury paradigm allowing precise evaluation of motor recovery and subsequent morphological evaluation of nerve regeneration in the same animals we compare functional recovery in adult mice that are mutant for specific genes that are thought to be important for regeneration. We have a special interest in molecules of the extracellular matrix (ECM).
Analysis of cellular functions
Loss of cells has a great impact on the whole organism not only during development but also for homeostasis, senescence and for pathogenesis. The specific ablation of cells in an otherwise intact, unaffected organism would make it possible to analyse cellular functions. Therefore, we have developed a novel strain of mice enabling us to specifically ablate any celltype (see also Fig. 1). The principle of this ablation mouse is the ubiquitous expression of a silenced toxin, which can be genetically activated in the offspring following mating with a recombinase expressing strain. The activation of the toxin may just be tissue-specific or additionally depending on agonist activation (e.g. tamoxifen).
Application 1: Screening for cell type specific genes
In an attempt to identify novel genes in oligodendrocytes we used our ablation mouse to deplete animals of all oligodendrocytes. These animals were then used in microarray expression profiling experiments. This effort resulted in the identification of several promising candidates, one of which is Ermin, a novel cytoskeletal molecule exclusively expressed by oligodendrocytes.
Application 2: Analysing specific functions of cell types in complex processes
The neuronal networks that generate vertebrate movements such as walking and swimming are embedded in the spinal cord. These networks, which are referred to as central pattern generators (CPGs), are ideal systems for determining how ensembles of neurons generate simple behavioral outputs. In spite of efforts to address the organization of the locomotor CPG in walking animals, very little is known about the identity and function of the spinal interneuron cell types that contribute to these locomotor networks. In a study where we specifically ablated V1 neurons, a class of local circuit inhibitory interneurons, we were able to show that these neurons shape motor outputs during locomotion and are required for generating “fast” motor bursting.
Application 3: Analysing cellular loss - impact on disease formation and progression
In multiple sclerosis (MS), non-remitting clinical disability is mainly caused by both neuronal and axonal damage, although oligodendrocytes, the myelinating glia of the CNS, are the primary target of the auto-immune-attack. Brain atrophy develops already in early stages of MS and appears to be influenced by previous inflammatory activity. The actual causes responsible for axonal and neuronal degeneration have not been undoubtedly identified, but inflammation or demyelination appear to be the driving forces. In order to discriminate between the neuronal damage caused by the inflammatory activity as opposed to the absence of oligodendrocytes we selectively ablated oligodendrocytes without any presence of inflammatory activity. Using this model, we show that axonal injury is the consequence of myelin disruption and does not require the adaptive immune system. We also provide evidence that efficient removal of myelin debris is important and benefits from a disrupted Blood-Brain-Barrier. Without this occurring, remyelination is poor and axonal damage increased. Our data therefore indicate that protecting axons from the consequences of myelin loss is critical, and that fostering efficient myelin clearance in concert with supporting remyelination is likely to be beneficial.
In sharp contrast to rapid repair after acute lung injury, chronic injury results in structural remodeling of lung tissue, commonly associated with chronic lung diseases, including asthma, chronic bronchitis, chronic obstructive pulmonary disease (COPD), and bronchiolitis obliterans syndrome (BOS). By specific and continuous depletion of Clara cells we have shown that they are critical airway progenitor cells and that chronic Clara cell depletion resulted in exhaustion of bronchiolar progenitor cell pools and peribronchiolar fibrosis. This model of chronic Clara cell depletion should be useful to study the pathogenesis of fibrosis after the loss of epithelial integrity, and should facilitate studies to promote epithelial regeneration and to prevent ineffective epithelial regeneration and aberrant tissue repair.
