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PhD: Genetic exploration of the carotid body: Unravelling mechanisms of neurogenic hypertension (NZ applicants only)


School of Medical Sciences

, Applications accepted all year round Funded PhD Project (Students Worldwide)

About the Project

Background:

Cardiovascular disease affects over 30% of people worldwide, and is the one of the leading causes of death each year. Cardiovascular diseases are commonly underpinned by hypertension, a complex and multifactorial disease. Evidence suggests that elevated sympathetic activity may be a key prognostic indicator and underlying causative factor of hypertension (1,2) although the reasons for sympathetic overactivity remain unknown (3,4). Nevertheless, a significant body of research suggests that the carotid chemoreflex plays a key role in elevating sympathetic drive contributing to disease pathophysiology (5,6).

We propose that specific subtypes of carotid body (CB) chemoreceptor type I cells transmit different types of sensory information to the brainstem via molecularly distinct reflex pathways. One convincing line of evidence for this hypothesis comes from the fact that multiple stimulants can activate glomus type I cells, including hypoxia, hypercapnia, acidosis, insulin, and angiotensin II yet not all glomus cells respond to all stimulants, suggesting some modality specificity within the CB. Given this, we propose that specific sensory stimuli act on sub-populations of glomus cells to switch on specific alternate reflex pathways, that in turn are connected to selective end organs.


The project:

The graduate student selected for this project will probe the intersection between structure and function in the CB, by leveraging cutting-edge approaches such as single cell RNA sequencing with immunohistochemistry to explore gene and protein expression within distinct cell types and specific microenvironments. If the student is interested, they may have the opportunity available to work closely with a specialist group in bioinformatics. Observations may be further examined using a range of state-of-the-art techniques such as single-cell live confocal imaging and digital droplet PCR. Our team also uses viral vectors to alter the expression of proteins of interest, providing a further opportunity for exploration.

The aim of this project is to identify whether these processes and / or molecular profiles are altered in hypertension, and to determine whether key markers are also present in human CBs. By obtaining CB tissue samples from humans, we hope to bridge the translational barrier from rodents to man. This is essential as it (i) supports the continued use of our rodent model for understanding mechanisms relevant to humans; (ii) informs onward human physiology studies and (iii) may reveal potential new therapeutic treatments.

This project is open to suggestions and we welcome all ideas.


Who we are looking for:

We are looking for a student who shares our passion in translational physiology and in tackling questions using a range of innovative approaches. The ideal candidate will be a creative, hard-working and curious individual; as well as adaptable, willing to learn, and passionate about driving their own research. We hope to find someone who enjoys working with others.

Anyone interested in conducting MSc (or other) research with us, please feel free to reach out as we may have alternative research opportunities available.


About us:

We are a small and diverse team of researchers who share an interest in answering biological questions with a multifaceted and translational approach. We look to tackle problems on a molecular, cellular, whole organ and physiological scale; and recognise the importance of leveraging a range of models and systems for hypothesis validation. Our research team is spearheaded by world-renowned translational physiologist Prof. Julian Paton, who has supervised over 20 PhD students over 30-years and will be the primary supervisor of this project. Please see the links below for some information about us and our current research highlights.

- https://www.fmhs.auckland.ac.nz/en/sms/about/our-departments/physiology/research-groups/translational-cardio-respiratory-research-laboratory.html
- https://www.hrc.govt.nz/news-and-events/finding-new-way-control-blood-pressure-gets-5m-funding-boost
- https://www.newstalkzb.co.nz/news/science/auckland-scientists-make-world-first-breakthrough-which-could-help-treat-dementia/
- https://unidirectory.auckland.ac.nz/profile/j-paton
- https://unidirectory.auckland.ac.nz/profile/emma-bardsley

Funding Notes

Unfortunately, due to COVID19 we can only accept NZ citizens, NZ residents or students currently residing in NZ at this time.

We welcome applicants with prior research experience, who have achieved a B+ or above in their undergraduate degree. For exceptional students with a GPA of 8.0 or above, the University of Auckland offers guaranteed doctoral scholarships. Exceptional Maori and Pacific students with a GPA of over 7.5 are also eligible for a guaranteed UoA scholarship.

- View Website


References

1. Bardsley EN, Paterson DJ. Neurocardiac regulation: from cardiac mechanisms to novel therapeutic approaches. J Physiol (Lond). October 2018. doi:10.1113/JP276962.

2. Briant LJB, Paton JFR, Pickering AE, Champneys AR. Modelling the vascular response to sympathetic postganglionic nerve activity. J Theor Biol. 2015;371(C):102-116. doi:10.1016/j.jtbi.2015.01.037.

3. Malpas SC. Sympathetic nervous system overactivity and its role in the development of cardiovascular disease. Physiol Rev. 2010;90(2):513-557. doi:10.1152/physrev.00007.2009.

4. Grassi G, Mark A, Esler M. The sympathetic nervous system alterations in human hypertension. Circ Res. 2015;116(6):976-990. doi:10.1161/CIRCRESAHA.116.303604.

5. Abdala AP, McBryde FD, Marina N, et al. Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat. J Physiol (Lond). 2012;590(17):4269-4277. doi:10.1113/jphysiol.2012.237800.

6. Pijacka W, Moraes DJA, Ratcliffe LEK, et al. Purinergic receptors in the carotid body as a new drug target for controlling hypertension. Nat Med. 2016;22(10):1151-1159. doi:10.1038/nm.4173.

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