You will earn 6 research credits over 6 weeks, conducting a faculty-supervised, hands-on, directed study research projects with results that will culminate in the preparation of a research paper. You will complete a minimum of 240 hours on research in and out of the laboratory.
Faculty mentors will work closely with you to direct your continued growth and knowledge development in the chosen research topic discipline.
| Course ID | Title | Credits | Syllabus |
|---|---|---|---|
| LONS RSLW 392S | International Independent Research in STEM Fields | 6 |
Mitochondrial dynamics (fission and fusion) alter in response to the energy needed by the cell; both processes become dysfunctional in the aging (neurodegenerative disease) as well as the developing (birth asphyxia) brain. This project aims to identify regulators of mitochondrial dynamics to enhance cell survival, and therefore neuroprotection, following neonatal brain injury.
Techniques: Cell culture, live cell microscopy, cell survival assays, western blot
Two key literature references:
1. Thornton C, Jones A, Nair S, Aabdien A, Mallard C, Hagberg H. Mitochondrial dynamics, mitophagy and biogenesis in neonatal hypoxic-ischaemic brain injury. FEBS Lett. 2018 Mar;592(5):812-830. doi: 10.1002/1873-3468.12943. Epub 2017 Dec 25. PMID: 29265370. https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.12943
2. Yang D et al Mitochondrial Dynamics: A Key Role in Neurodegeneration and a Potential Target for Neurodegenerative Disease Front Neurosci (2021) doi.org/10.3389/fnins.2021.654785 https://www.frontiersin.org/articles/10.3389/fnins.2021.654785/full
Both diabetes and disturbed flow are known to promote endothelial dysfunction (e.g. proinflammatory signaling and increased permeability) which contribute to the development of cardiovascular disease. This project will explore whether hyperglycaemia, hyperlipidaemia, and/or hyperinsulinemia worsens endothelial function in cells exposed to disturbed flow.
Techniques: endothelial cell culture, western blot, qPCR, immunostaining
Two key literature references:
1. Sena et al. Endothelial dysfunction – a major mediator of diabetic vascular disease, Biochimica et Biophysica Acta
2013;1382(12):2216.https://www.sciencedirect.com/science/article/pii/S0925443913002718
2. Chui & Chien. Effects of disturbed flow on vascular endothelium. Physiological Reviews, 2011;91(1):327.
The Neuronal Ceroid Lipofuscinoses (NCL) are a set of inherited neurodegenerative disease in children that cause premature death. Recently, certain lipids have been shown to accumulate in many NCLs and some of them may be useful biomarkers. We have developed some models of some NCLs and hypothesise that they will also accumulate the lipids in their lysosomes. We will test this by incubating the zebrafish disease models (and control siblings) in vital dyes to visualise the lipids. The data will be captured using fluorescent imaging. If time allows, we will see if the staining is returned to normal when treated with potentially therapeutic drugs.
Techniques: Husbandry and breeding of zebrafish. Culture of zebrafish embryos and larvae. Treatment of zebrafish embryos and larvae with vital dyes. Fluorescent imaging. Quantification. Statistics. Exposure to UK licensing of animal experimentation.
Two key literature references:
1. Wager K, Zdebik AA, Fu S, Cooper JD, Harvey RJ, Russell C. Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease). PLoS One. 2016;11(6):e0157365. https://doi.org/10.1371/journal.pone.0157365
2. Mahmood et al. (2013). A zebrafish model of CLN2 disease is deficient in tripeptidyl peptidase 1 and displays progressive neurodegeneration accompanied by a reduction in proliferation. Brain 136:1488-507. doi: 10.1093/brain/awt043.
This project will investigate how metabolic hormones such as insulin affect the function of the immune cells such as macrophages, and how in turn this may impact diabetes and its comorbidities such as cardiovascular disease – which are huge socio and economic burdens to our society.
Techniques: Cell culture (primary cells and cell lines), DNA extraction + PCR, RNA extraction + RT-qPCR, Protein: Immunoblotting + ELISA
Two key literature references:
1. Batty MJ, Chabrier G, Sheridan A, Gage MC, Metabolic Hormones Modulate Macrophage Inflammatory Responses, Cancers 2021, 13(18), 4661; https://doi.org/10.3390/cancers13184661
2. Chabrier G, Hobson S, Yuldasheva N, Kearney M, Schurmans S, Pineda-Torra I, Gage MC (2018). Aged insulin resistant macrophages reveal dysregulated cholesterol biosynthesis, a pro-inflammatory profile and reduced foam cell capacity. PREPRINT www.biorxiv.org https://doi.org/10.1101/467118
We have generated a new knock-out zebrafish line lacking receptors important for cardiovascular development. The fish are bred on a fluorescent reporter background and their vessels express a red fluorescent protein. The student will help analyse images obtained on the confocal microscope and report in details how the how the heart and vasculature develop in comparison to wild-type fish.
Techniques: Fluorescent stereomicroscopy and analysis of confocal images using ImageJ.
Two key references:
1. Gore AV, Monzo K, Cha YR, Pan W, Weinstein BM. Vascular development in the zebrafish. Cold Spring Harb Perspex Med. 2012 May;2(5):a006684. doi: 10.1101/cshperspect.a006684. PMID: 22553495; PMCID: PMC3331685.
2. Fantin A, Lampropoulou A, Gestri G, Raimondi C, Senatore V, Zachary I, Ruhrberg C. NRP1 Regulates CDC42 Activation to Promote Filopodia Formation in Endothelial Tip Cells. Cell Rep. 2015 Jun 16;11(10):1577-90. doi: 10.1016/j.celrep.2015.05.018. Epub 2015 Jun 4. PMID: 26051942; PMCID: PMC4528263.
A key question in cell and developmental biology is how the mammalian embryo is assembled. Developmental fates are controlled by the regulation of gene expression, and miRNAs play an important part in this. These small, double-stranded RNAs of approximately 22 nucleotides act by post-transcriptionally suppressing gene expression. They operate to fine-tune expression levels, and their importance is exemplified by their absence, which results in lethality of the early embryo. We wish to understand the function of miRNAs in the early embryo by testing their regulation of specific genes involved in the initial developmental programme.
Techniques used: The student will learn core techniques in molecular biology including mammalian cell culture, protein extract preparation, and Western blotting.
Reference:
Montelukast is a leukotriene receptor antagonist with potential to be repurposed as a neuroprotective agent for preterm infants. One possible mechanism of action is that Montelukast acts on the cerebral endothelial cells, protecting the developing brain from inflammation.
Techniques used: Cell culture, ELISA, dose response pharmacology, RNA extraction and qRT-PCR, immunocytochemistry
Reference:
The following information is vetted and provided by the American Association of Collegiate Registrars and Admissions Officers (AACRAO) on the Electronic Database for Global Education (EDGE).
| Percentage | Description | U.S. Equivalent |
| 70 – 100% | First Class | A |
| 60 – 69% | Second Class Upper | B+ |
| 50 – 59% | Second Class Lower | B |
| 40 – 49% | Third Class/Pass | C |
| 0 – 39% | Fail | F |