Project title: Identification of a novel signalling pathway triggering abnormal mitosis and neuronal death in Alzheimer brains
Reference: 18-19-005
Earliest available start date: 01 January 2020
Direct of Studies: Dr Torsten Bossing
2nd Supervisor: Dr Claudia Barros
3rd Supervisor: Dr Jon Gil-Ranedo
Project information
In healthy brains mature nerve cells never divide. In contrast, brain damage caused by Alzheimer Disease forces mature nerve cells to divide, leading to their death. If we can understand what causes these nerve cells to divide, we may be able to prevent their death.
The fruitfly is a favourite animal model to study the molecular causes of Alzheimer symptoms. In fruitflies the expression of defective human Tau proteins, the cause of family related Alzheimer cases, results in disruptions of microtubules, molecules that are major building blocks of every cell. Our findings indicate that this damage drives division in nerve cells by activating the NfkappaB signalling pathway. This pathway exists in humans and has been implicated in Alzheimer disease. We also found that NfkappaB signal is abnormally active in dividing mature nerve cells in post-mortem brains of Alzheimer sufferers. Our findings strongly suggest that defective Tau in the brains of Alzheimer patients disturbs microtubules, which abnormally activate the NfkappaB signal forcing nerve cells to enter into division and to die. Yet, the link between Tau, microtubules destruction and NfkappaB signalling is unknown. We propose to use fruitflies and post-mortem human brains to identify the molecules abnormally activated by aberrant Tau. The identified molecules may serve as future drug targets allowing prevention or at least amelioration of neuronal death in Alzheimer diseased brains.
The prospective postgraduate student will have daily guidance from the Director of Study and will be encouraged to develop his/her scientific ideas to actively contribute to the development of work directions and priorities. He/She will also be in constant interaction with other groups that share the main open-spaced research laboratories at Faculty of Health. He/ She will have the opportunity to exchange ideas with students and staff in open space postgraduate offices, participate in a variety of seminar programmes (e.g. weekly research progress seminar series; monthly departmental PhD student-led journal club) and will be encouraged to attend at least 1 international scientific meeting. The student will be trained in a wide range of molecular and cellular laboratory techniques, spanning in vivo Drosophila work to human tissues. He/she will also be trained by the supervisors towards enhancement of presentation skills and public speaking (e.g. via lab meeting presentations and preparation for other oral presentations). In addition, the student will participate in courses from the Plymouth University Graduate Skills Program promoting the development of postgraduate academic and transferable expertise such as scientific writing and critical thinking. In summary, the prospective postgraduate student will be in a high quality scientific and educational environment and will have the support to successfully complete his/her doctoral studies and progress in his/her career.
For further information regarding the project, please contact Dr Torsten Bossing. However, applications must be made in accordance with the details shown below.