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 |
Different culture medium additives have been proposed to increase the proportion of endothelial cells versus other vascular cell types in mixed vascular cultures. Culturing equine endothelial cells is hampered by contamination by vascular smooth muscle cells. This project will investigate the effectiveness of different culture medium additives on the purity of equine endothelial cell cultures.
Techniques: Cell culture, immunofluorescence, Western blotting, qPCR
Two key literature references:
1. Phenotypic and functional characterization of equine endothelial cells.
Elizabeth J. Finding; Robert Purcell; Nicola Menzies-Gow; Jonathan Elliott; Caroline Wheeler-Jones
2020 ACVIM Forum On Demand Research Abstract Program. J Vet Intern Med, 34: 2961-2962. https://doi.org/10.1111/jvim.15904
2. Microvascular endothelial cells from the heart by H.M. Piper, R. Spahr, S. Mertens, A. Krützfeldt, and H. Watanabe. p 158-177 in ‘Cell culture techniques in heart and vessel research’ by H.M. Piper 1990, Springer-Verlag. DOI: 10.1007/978-3-642-75262-9_11
This project will use our in vitro laboratory models to determine if horse tendon cells remember an inflammatory event and if that affects their response to future inflammation.
Techniques: cell culture, immunocytochemistry, qPCR.
Two key literature references:
1. McClellan, A., Evans, R., Sze, C., Kan, S., Paterson, Y., and Guest, D.J. (2019). A novel mechanism for the protection of embryonic stem cell derived tenocytes from inflammatory cytokine interleukin 1 beta. Scientific Reports 9(1), 2755.
2. Paterson, YZ, Cribbs A, Espenel M, Smith EJ, Henson FMD, Guest DJ (2020). Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes. Stem Cell Res Ther. 11 (1):184.
This project will use cell-based models to identify the role of novel genes in bone regeneration.
Techniques: cell culture, immunocytochemistry, qPCR
Two key literature references:
1. Blott SC, Swinburne JE, Sibbons C, Fox-Clipsham LY, Helwegen M, Hillyer L, Parkin TD, Newton JR, Vaudin M: A genome-wide association study demonstrates significant genetic variation for fracture risk in Thoroughbred racehorses. BMC genomics 2014, 15(1):147.
2. Baird, A., Lindsay, T., Everett, A., Iyemere, V., Paterson Y. Z., McClellan, A., Henson, F.M.D. & Guest, D. J. (2018) Osteoblast differentiation of equine induced pluripotent stem cells. Biology Open. doi: 10.1242/bio.033514. 10;7(5).
This project aims to compare three methods for parthenogenetic activation of cat oocytes after in vitro maturation. Results from this study will be applicable to development of strategies for conservation of endangered feline species. The embryos will be cultured in a time-lapse microscope to image and determine pattern of cell division and duration between cell cycles until blastocyst stage.
Techniques: Isolation of oocytes from cat spayed cat ovaries, grading oocytes quality, preparation of culture media for sterile culture of oocytes and embryos, determining nuclear stage in meiosis following in vitro maturation of oocytes, chemical activation of oocytes to produce embryos, culture of embryos in Embryoscope to get dynamics of cell division in cat oocytes until blastocyst stage.
Two key literature references:
1. Peter Freistedt, Miodrag Stojkovic, and Eckhard Wolf (2021) Efficient In Vitro Production of Cat Embryos in Modified Synthetic Oviduct Fluid Medium: Effects of Season and Ovarian Status BIOLOGY OF REPRODUCTION 65, 9–13.
2. Suresh Dinkar Kharche and Hemant Shankar Birade (2013) Parthenogenesis and activation of mammalian oocytes for in vitro embryo production: A review. Advances in Bioscience and Biotechnology 4, 170-182.
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 fusion 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
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:
He, L., & Hannon, G. J. (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nature Reviews Genetics, 5(7), 522–531.
Diabetic vasculopathy is a significant factor in the development of diabetes-linked cardiovascular disease. Animal models of early and advanced diabetes are widely used in research, however, characterisation of vascular changes within many target organs remains limited in these models. Therefore, this project will look to characterize the vascular changes occurring within a number of major organs of HFSD fed mice.
Techniques: Histology, immunofluorescence, imaging
Two key literature references:
1. Choi et al. (2022) Animal models of diabetes-associated vascular diseases: an update on available models and experimental analysis. Br J Pharmacol.179: 748–769.
2. Faulkner, A. et al. (2020) Multi-omics analysis of diabetic heart disease in the db/db model reveals potential targets for treatment by a longevity-associated gene. Cells 9 (5): 1283.
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
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 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.
CLN2 disease is a lysosomal storage disorder. The zebrafish model of CLN2 disease displays neurodegeneration and epilepsy akin to that seen in patients. In this zebrafish model, apoptotic bodies appear to be engulfed by microglia in the brain, but the microglia also have lysosome dysfunction so cannot destroy the engulfed apoptotic bodies. Activation of the sigma 1 receptor limits microglial activation and improves neuronal health in some model systems. We have preliminary data suggesting that Sigma 1 receptor modulation does not significantly affect microglia size or number. We next want to see if Sigma 1 receptor modulation affects the size or number of apoptotic bodies. We hypothesize that sigma 1 receptor modulation in the zebrafish model of CLN2 disease will alter the numbers of apoptotic bodies.
Techniques: Husbandry and breeding of zebrafish. Culture of zebrafish embryos and larvae. Treatment of zebrafish embryos and larvae with sigma 1 agonists. TUNEL assay for apoptotic bodies. Brightfield imaging. Quantification. Statistics. Exposure to UK licensing of animal experimentation.
Two key literature references:
1. Moritz et al. (2015). Live imaging reveals a new role for the sigma-1 (σ1) receptor in allowing microglia to leave brain injuries. Neuroscience Letters 591: 13-18. https://doi.org/10.1016/j.neulet.2015.02.004.
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.
Extracellular vesicles are small particles released from cells into all bodily fluids including milk. They contain cargo including mRNA, microRNA, DNA and proteins and can be taken up by recipient cells. Our previous studies have shown that cows’ milk contains EV that can be taken up by human monocytes and influence inflammatory responses. The aim of this study is to determine whether EV isolated from sheep and goat milk have similar properties.
Techniques: Ultracentrifugation, cell culture, flow cytometry, ELISA, RNA isolation, RT-PCR.
Two key literature references:
1. Pollott G, Brito A, Gardiner C, Lawson C. A Comparison of Different Methodologies for the Measurement of Extracellular Vesicles and Milk-derived Particles in Raw Milk from Cows. Biomarker Insights. 2016 13;11:147-155. doi: 10.4137/BMI.S38438.
2. Pollott GE, Wilson K, Jerram L, Fowkes RC, Lawson C. Technical note: A non-invasive method for measuring mammary apoptosis and epithelial cell activation in dairy animals using microparticles extracted from milk. J Dairy Sci. 2014 97(8):5017-22
Tart cherry juice extract has been reported to have anti-inflammatory and antioxidant properties. Extracellular vesicles are small particles released from cells including from plants. They contain cargo including mRNA, microRNA, DNA and proteins and can be taken up by recipient cells. The aim of this study is to determine whether extracellular vesicles isolated from tart cherry extracts alter monocyte inflammatory responses, in vitro.
Techniques: Ultracentrifugation, cell culture, flow cytometry, ELISA
Two key references:
1. Heinrich LF, Andersen DK, Cleasby ME, Lawson C. Long-term high fat feeding of rats results in increased numbers of circulating microvesicles with pro-inflammatory effects on endothelial cells. Br J Nutr. 2015 113(11):1704-11.
2. C Lawson, J Vicencio, D Yellon S Davidson; Microvesicles and exosomes - new players in metabolic and cardiovascular disease, Journal of Endocrinology; 2016 228(2):R57-71. doi: 10.1530/JOE-15-0201.
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 |