Why don't all blood vessels behave the same way? A proteomic, transcriptomic and functional “Rat map” of vascular tissue

Description

The contraction and dilation of blood vessel controls the flow of blood, and the oxygen/nutrients contained within, to the tissues to match the metabolic demand. When exercising, blood vessels supplying skeletal muscle respond to the sympathetic drive and adrenaline release by dilating, therefore providing more blood flow to the muscle with increased metabolic demand. Conversely, arteries supplying blood to the gut undergo vasoconstriction to the same stimuli to reduce blood flow in an area that is not as vital during exercise. This differential response of the vasculature to the same stimuli suggests that blood vessels are not the same and may express different combinations of receptors, ion channels and signalling molecules.

These differences are potentially very important for us in terms of understanding how blood flow is controlled to match tissue demand, and eventually will lead to investigations of how this might break down in disease states. To begin with, this project will focus on healthy tissue, however this could be expanded to look in disease models, such as the spontaneously hypertensive or diabetic rat models.

To investigate the differences between vascular beds, our group has undertaken a transcriptomic profile of three vascular beds, the aorta, mesenteric and pulmonary arteries. From this data library, we have identified stark differences in the mRNA for different receptors, channels and signalling molecules between different vascular beds. Remarkably, we have also shown that within the vascular tree for mesenteric arteries there are differences between 1^st, 2^nd, 3^rd and 4^th order vessels. These findings suggest that not only are the vascular beds different from each other, but within the vascular bed there are marked differences in the expression of vasoconstriction and dilation-linked receptors that can be measured as differences in contractile behaviour.

In this project, the student will carry out further investigations of the transcriptomic data, adding further vascular beds to our data set with a view to this becoming an online repository for information to be shared with the wider community; the “Liverpool Rat Map”. The student will also carry out mass spec-based proteomic analysis of the vascular beds to demonstrate that protein levels of our identified targets are changed. These data will be confirmed using qPCR and western blotting where feasible. Using wire myography, patch clamp recording, Seahorse analyser and cellular fluorescence imaging, the functional differences of differences in receptor expression and metabolic profile will be investigated to provide functional evidence for the effects of the expression changes within the tissue.

Student experience

The successful student will gain full training in a multitude of techniques, ranging from cell culture, electrophysiology measurements, NMR Metabolomics, fluorescence imaging, metabolic analysis using Seahorse analyser technology, and essential research skills including western blotting, qPCR, immunofluorescence, and ELISA. All techniques are established in the laboratory groups of the supervisory team.

Applicant Information

All postgraduate students undertake the Post Graduate Researcher (PGR) Development Programme which aims to enhance their skills for a successful research experience and career. They are required to maintain an online record of their progress and record their personal and professional development throughout their research degree. The Liverpool Centre for Cardiovascular Science holds monthly research group meetings where students are given opportunities to present their research and meet and interact with their peers and senior researchers. Students are also encouraged to attend the seminar series to gain a breadth of knowledge from related research within the Department of Cardiovascular and Metabolic Medicine and wider research themes across our Institute.

The Institute of Life Course and Medical Science is fully committed to promoting gender equality in all activities. In recruitment we emphasize the supportive nature of the working environment and the flexible family support that the University provides. The Institute holds a Gold Athena SWAN award in recognition of on-going commitment to ensuring that the Athena SWAN principles are embedded in its activities and strategic initiatives.

Application is via CV and cover letter to the Project Supervisor email richard.rainbow@liverpool.ac.uk