LACI-Hunt: A systematic and continuous approach to drug identification and selection to prevent and treat vascular causes of dementia.

Based in the Edinburgh CAMARADES group (www.camarades.info), the student will develop efficient methods to systematically and continuously search public databases and analyse scientific literature to find new drug targets, re-purposable and novel drugs for testing in future preclinical and clinical trials. The work will involve 2 key tasks, building on experience from other disease areas.

First, the candidate will develop a Systematic Online Living Evidence Summary[1] to identify, annotate and curate published information from in vivo and in vitro research, as well as validating the performance of each of these stages. This work will build on the existing SOLES architecture (https://github.com/camaradesuk/solesR), but will require work to adapt these tools for the cerebral small vessel disease literature such as identification of specific models and outcome measures.

Secondly, the candidate will develop a pipeline to combine these data with other sources of information including target, pathway and network analysis platforms, drug and chemical databases, and clinical trial registries, to provide an exhaustive and continually updated summary of current knowledge to inform drug selection for clinical trial. This approach has been used to inform drug selection in the MND-SMART trial (Lancet Neurology, forthcoming), but again will need adaption for use in cerebral small vessel disease.

Both of these tasks involve a series of discrete components, and there will be opportunities to refine existing or develop novel components, which might have more general applicability beyond LACI-Hunt.

The successful candidate is likely to have a 1st or 2:1 honours degree in biomedical sciences or related subject. Prior experience in neuroscience and/or data science would be an advantage. An MSc in a related discipline would also be an advantage but is not essential. Please apply via the Edinburgh Neuroscience weblink.

Training outcomes:

·       Interdisciplinary working

·       Systematic review

·       Automation and machine learning

·       Reproducibility and rigour in research

·       Statistics and computational skills

Website: www.camarades.info

             www.ed.ac.uk/clinical-brain-sciences/research/row-fogo-centre

Race Against Dementia: All Hands Team Vascular

Vascular causes of dementia are common. Cerebral small vessel disease (cSVD) is the leading cause of vascular cognitive impairment (VCI) and vascular dementia (VaD) including in mixed dementias with Alzheimer’s disease. Despite causing up to 45% of dementias, research and established treatments for vascular causes of dementia are lacking. Race Against Dementia (RAD): Team Vascular – Prevention and Treatment of Vascular Cognitive Impairment and Dementia is a cross-disciplinary team working together to prevent and treat vascular causes of cognitive impairment and dementia, with expertise in cSVD, Alzheimer’s disease and dementia, clinical research including trials, discovery science, and data science including experimental validity, literature and drug data interrogation. The Team comprises four interconnected workstreams: LACI-Cog, a pilot trial in patients with cognitive decline; LACI-Rat, conducting randomised trials in preclinical rodent models; LACI-Hunt, to develop efficient methods of searching for new drug targets and drugs; and LACI-Ignite, to advocate for the importance of vascular causes of dementia, foster awareness, and promote interest amongst early career and senior researchers, funders and policy-makers.

PhD studentships

This is one of three RAD Team Vascular PhDs. In these three-year PhDs, students will work in a multidisciplinary environment and receive specific training in cerebrovascular disease including vascular causes of dementia via local, national and international research collaborations and general training via the PostGraduate Office. The training is designed to ensure students gain a broad range of skills that will enhance their employability and ensure they can become future leaders in research.

Supervisors and Environment

All supervisors are experienced researchers, bring complementary skills to tackle vascular causes of cognitive decline and dementia, and world leading in their respective topics. They are all trained in PhD regulations, Equality & Diversity and Unconscious Bias, student mentoring and training, and are approved by the UoE to be a supervisor.