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.
|LONS RSLW 392S||International Independent Research in STEM Fields||6|
|Cell Biology/Development||Camden||microRNA regulation of embryonic cell development|
|Cell Biology/Development||Camden||What is the pattern of cell death in the zebrafish model of Late Infantile Neuronal Ceroid Lipofuscinosis, an inherited neurodegenerative disease?|
|Cell Biology/Immunology||Camden||Can extracellular vesicles isolated from cows milk affect human immune cell responses in vitro|
|Large Animal Medicine||Hawkshead||Efficacy of drug treatment on zoonotic schistosomes in livestock|
|Large Animal Medicine||Hawkshead||Are Diabetic Dogs Hypercoagulable? Assessment of thrombotic risk via thromboelastography|
|Large Animal Medicine||Hawkshead||Subtle changes in equine behaviour and their relation with chronic disease|
|Large Animal Medicine||Hawkshead||Characterising microvesicles from equine mesenchymal stem cells as a novel therapeutic strategy|
|Large Animal Medicine/Parisitology||Hawkshead||Zoonotic transmission of schistosomiasis in West Africa|
|Neuroscience/Cell Biology||Camden||Montelukast as a therapy for perinatal brain injury|
|Neuroscience/Cell Biology||Camden||Breaching the blood-brain-barrier: protecting astrocytes from liver disease|
|Neuroscience/Cell Biology||Camden||How do endocrine disrupting chemicals contribute to pituitary tumour development?|
|Physiology/Cell Biology||Camden||Does upregulation of AMPK activity ameliorate muscular dystrophy?|
|Physiology/Cell Biology||Camden||Do extracellular vesicles play a role in vascular inflammation in hyperglycaemia|
|Physiology/Cell Biology||Camden||Do Sulf1/Sulf2 modulate ischemic recovery in a positive or negative manner by cell signalling regulation?|
|Physiology/Cell Biology||Camden||Understanding the role of phosphate in vascular calcification|
|Physiology/Cell Biology||Camden||Breast cancer cell “stemness”: is this regulated by HUNK signalling.|
|Physiology/Cell Biology||Camden||Identifying Cellular Mechanisms for the Skeletal Benefits of SFX-01|
|Physiology/Cell Biology||Camden||The role of in vivo modulation of mechanical signals|
|Reproductive Physiology/Cell Biology||Camden||The role of FSTL3 during male reproductive ageing|
microRNA regulation of embryonic cell development
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.
What is the pattern of cell death in the zebrafish model of Late Infantile Neuronal Ceroid Lipofuscinosis, an inherited neurodegenerative disease?
Late infantile neuronal ceroid lipofuscinosis (NCL) is a fatal inherited childhood neurodegenerative disease. It is not clear what the earliest events are in the disease are, and which events occur subsequently .We have observed that the zebrafish mutant model of this disease has apoptosis. To understand the pathology better we will investigate the spatio-temporal pattern of apoptosis prior to an overt phenotype.
Can extracellular vesicles isolated from cows milk affect human immune cell responses in vitro
The project will seek to determine whether extracellular vesicles isolated from milk collected from cows at different stages of lactation have similar, magnified or opposing effects on human monocyte activation in vitro.
Efficacy of drug treatment on zoonotic schistosomes in livestock
Schistosoma spp. are the causative agents of schistosomiasis, a prevalent, chronic and debilitating helminthic disease of humans and animals across much of the developing world. Schistosoma spp. have an asexual stage occurring in an intermediate host freshwater snail and the sexual stage of these dioecious parasites within a definitive mammalian host. Recent environmental changes increase the opportunities for schistosome species of humans and animals to be found in the same geographical area and in the same host type and is predicted to further influence the potential for novel zoonotic hybrid parasites. These zoonotic schistosomes have been found infecting both humans and livestock definitive hosts and snails intermediate hosts despite high coverage mass drug administration with praziquantel, which currently represents the only available drug for treatment of schistosomiasis. Our project aims to elucidate the epidemiology of these novel zoonotic hybrid schistosomes and the impact of parasite hybridisation on host spectrum, praziquantel efficacy, host morbidity and ultimately transmission potential.The student will examine the prevalence and intensity levels and molecularly characterize Schistosoma species circulating in livestock in Senegal before and after treatment with praziquantel.
Are Diabetic Dogs Hypercoagulable? Assessment of thrombotic risk via thromboelastography
People with diabetes mellitus are at increased risk of complications relating to thrombosis or strokes. Although there are many similarities between dogs and people with diabetes, we don’t appreciate an increased risk of thrombosis in diabetic dogs. It would be therefore important to establish whether dogs with diabetes mellitus are similarly affected (ie, hypercoagulable) as assessed by thromboelastography and if not, what is reducing their risk of thrombosis? This is a clinical investigation and will use residual blood from dogs seen at the Queen Mother Hospital for Animals (small animal referral hospital) with diabetes mellitus. Each enrolled dog will have a thromboelastograph performed with and without t-PA to investigate for the presence of abnormal coagulation status.
Subtle changes in equine behaviour and their relation with chronic disease
Many chronic health conditions experienced by horses (such as lameness or inflamed skin) can be recognised by clinical signs, whilst others (such as gastric ulceration) are harder to detect but, in both cases, severity of clinical sign does not reliably map to equine subjective experience. The overall impact of such conditions on equine welfare and quality of life needs to be better understood. The summer student will work alongside a post-graduate student project examining the relation between clinical signs of disease severity and equine behaviour. A key part of the project is to record behaviour in a more structured and fine-grained manner than usual, both by direct observation, analysis of video recording and interpretation of output of non-invasive automated behavioural monitors. The work will provide a potential platform for veterinarians and owners to make use of the findings from this project in routine assessments of equine welfare.
Characterising microvesicles from equine mesenchymal stem cells as a novel therapeutic strategy
Mesenchymal stem cell therapy has shown beneficial outcomes for the treatment equine tendon injuries. However, their mechanism of action needs to be better understood in order to improve regenerative strategies using this technology. One mechanism appears to be paracrine activity involving microvesicles (MVs). MVs are cell membrane bound particles shed by the cells and contain a cargo of effector molecules such as microRNAs which likely help in the resolution of inflammation in the injury. However this hypothesis needs to be tested and the key question that will be addressed in this project is: Can microvesicles derived from equine bone marrow mesenchymal stem cells (MSCs) induce a pro-resolution (repair) phenotype in tendon cells? MVs will be prepared from MSCs and their ability to modulate resolution pathways in tendon cells will be investigated in an in vitro model of tendon inflammation using a number of techniques listed above.
Zoonotic transmission of schistosomiasis in West Africa
Schistosoma spp. are the causative agents of schistosomiasis, a prevalent, chronic and debilitating helminthic disease of humans and animals across much of the developing world. Schistosoma spp. have an asexual stage occurring in an intermediate host freshwater snail and the sexual stage of these dioecious parasites within a definitive mammalian host. Recent environmental changes increase the opportunities for schistosome species of humans and animals to be found in the same geographical area and in the same host type and is predicted to further influence the potential for novel zoonotic hybrid parasites. These zoonotic schistosomes have been found infecting both humans and livestock definitive hosts and snails intermediate hosts despite high coverage mass drug administration with praziquantel, which currently represents the only available drug for treatment of schistosomiasis. Our project aims to elucidate the epidemiology of these novel zoonotic hybrid schistosomes and the impact of parasite hybridisation on host spectrum, praziquantel efficacy, host morbidity and ultimately transmission potential. The student will examine the prevalence and intensity levels and molecularly characterize Schistosoma species circulating in livestock and human populations in Niger before and after treatment with praziquantel.
Montelukast as a therapy for perinatal brain injury
Brain injury following preterm birth is highly associated with inflammation. Currently there are very few therapies that help to limit injury in the at-risk patients; conventional anti-inflammatory agents have been shown to produced mix results. As an alternative, we have identified Montelukast as a potential therapy to protect against brain injury early in life. Our preliminary experiments in a mouse model of perinatal brain injury show that Montelukast can reduce inflammation in the body and in the brain, and can reduce some signs of brain injury. The aim of the current study is to understand how much of the administered drug reaches the brain, and what effect it has on the normal and abnormal development of each neural cell population. We will produce primary cultures of neurons, astrocytes, microglia and oligodendrocytes, and test the dose dependent response of these cell populations to Montelukast treatment. These findings will facilitate future studies with Montelukast, including translation to clinical trials, allowing a dosing regime to be identified that has the maximum capacity to be effective.
Breaching the blood-brain-barrier: protecting astrocytes from liver disease
Humans and companion animals with liver disease suffer from an associated neurological complication called hepatic encephalopathy, that causes mood changes, uncoordinated movement, brain swelling, seizures, coma and (eventually) death. Unfortunately, the drugs used to treat these severe clinical signs are also toxic to the liver. Therefore, this project examines the possible role for natriuretic peptides (locally produced peptide hormones, particularly C-type natriuretic peptide (CNP)) in protecting astrocytes and endothelial cells in the blood-brain-barrier, from the toxic effects of ammonia and other compounds produced in these patients. As CNP is not hepatotoxic, and is the most active natriuretic peptide of the central nervous system, it is a promising candidate as a novel therapy.
How do endocrine disrupting chemicals contribute to pituitary tumour development?
Pituitary tumours are the most common form of intracranial tumour, affecting 1 in 6 humans by the time of their deaths. One subtype of these tumours leads to excess growth, due to the over production of growth hormone. This condition - called Acromegaly - is also seen in the domestic cat population, with an incidence almost ten times that seen in humans. Interestingly, patients (human and feline) with acromegaly also have elevated serum levels of chemicals used in plastics, that are known to be endocrine disrupting chemicals (EDCs). Therefore, this project will examine the effects of four of these EDCs on pituitary tumour cell lines, to determine the mechanisms by which these chemicals may either increase cell growth, cell survival, and increase the expression and secretion of growth hormone.
Does upregulation of AMPK activity ameliorate muscular dystrophy?
Duchenne muscular dystrophy is a fatal X-linked muscle wasting disease caused by mutations in the DMD gene. Although improved medical management has increased quality of life and longevity, nothing currently prevents the inexorable loss of muscle function associated with muscle fibre loss and fibrosis. A wide range of novel therapies are under development ranging from gene therapy with a dystrophin minigene though to pharmaceutical agents that address some aspects of the downstream pathology arising from dystrophin deficiency. AMP-activated protein kinase (AMPK) is a master metabolic sensor in cells and an on-switch for the autophagy-mitophagy pathway. Given its key role in cellular metabolism it has been speculated that increased activation of AMPK may be a potential treatment option for DMD. However, all experiments to date to test this concept have used a non-specific activator of AMPK (AICAR) and thus we do not know if the beneficial effects seen in mice are solely due to AMPK activation. We will use a novel transgenic mouse that expresses a high activity mutant of AMPK to model the effect of treatment with specific activators of AMPK. We will cross this novel transgenic with the dystrophic mdx mouse to assess the effects of specific activation of AMPK in a murine model of DMD. We will use muscle physiology as the functional assessment and a combination of histopathology and molecular biology to assess the effects of increased AMPK activity in post-mortem muscle samples.
Do extracellular vesicles play a role in vascular inflammation in hyperglycaemia
The project will seek to determine whether extracellular vesicles which are released from hyperglycaemic endothelial cells cause inflammatory responses in endothelium in vitro.
Do Sulf1/Sulf2 modulate ischemic recovery in a positive or negative manner by cell signalling regulation?
The delivery of oxygen and nutrients by blood vessels is essential for survival of all tissues. Damage or blockage of a blood vessel if not fatal leads to tissue ischaemia that activates a stress response with a potential to trigger recovery by attempting to re-vascularise the ischemic tissue. The process of revascularisation is triggered by angiogenesis, a process characterised by growth of endothelial cells. There are, however, many in vivo inhibitors that prevent such initial step of re-vascularisation by preventing endothelial cell growth. There are also some angiogenic growth factors that can promote angiogenesis. Most inhibitors as well as growth promoters, however, are heterogeneous and therefore do not always produce their desired effects. We hypothesise that the complexity of angiogenesis does not only relate to the complexity of some known modulators of angiogenesis but also the key role played by sulfation patterns of co-receptors required for cell signalling cascades. We hypothesise that Sulf1 and Sulf2 play differential roles during ischemic injury as our in vitro analysis shows up-regulation of Sulf2 but down-regulation of Sulf1 in an HMEC1 cells, an endothelial cell line under hypoxia. The key aim of the present project is to determine the nature of cell signalling pathways that are activated under hypoxia and whether those pathways are protected or inhibited by Sulf1 and Sulf2 activation.
Understanding the role of phosphate in vascular calcification
Having vascular calcification significantly increases the risk of having an adverse cardiovascular event such as a heart attack or stroke. At present there are no treatments to prevent or reverse vascular calcification. The aim of this project will be to examine how elevated extracellular phosphate levels, as seen in vascular calcification, affect the function of vascular smooth muscle cells (the cell type involved in vascular calcification). This in vitro project will use human vascular smooth muscle cells and a number of established experimental assays to answer the research question.
Breast cancer cell “stemness”: is this regulated by HUNK signalling.
NK is a kinase that is known to be expressed at high levels in a number of aggressive cancers. This kinase can activate a number of intracellular signalling pathways and in mammary cancer it’s overexpression promotes resistance to therapy. One of the pathways that can be activated is YAP/TAZ and in some cancer types this can enhance stemness of the cells. As increased stemness is known to result in resistance to therapy we hypothesise that the Resistance to therapy in HUNK expressing mammary cancer cells is a consequence of increased stemness due to activation of YAP and/or TAZ. We aim to test this hypothesis using gain and loss of function of both HUNK and YAP/TAZ signalling pathways coupled with mammosphere assays to measure stemness of the cells.
Techniques utilized: Mammosphere assays, gene silencing by RNAi, cell survival assays
Identifying Cellular Mechanisms for the Skeletal Benefits of SFX-01
We will examine how SFX-01 (stable form of sulforaphane) modulates the bone cell behavior and potentially if it modulates that natural OA that develops in STR/Ort mice. We will first assess the effect of SFX-01 on osteoclast and osteoblast function (using control/healthy mice). For Osteoclast cultures, long bones will be derived from 6-8 weeks old mice and will be treated with different concentration of sfx-01 in order to measure the number of osteoclast and bone resorption at each dose (by transmitted and reflective light microscopy) . Also osteoblasts will be derived from calvarian bones and treated with sfx-01 so to measure the bone formation by image analysis. Finally, SFX-01 targeting of osteoclasts, osteoblasts in STR/Ort mice will be assessed.
Techniques utilized: Cell culture, bone resorption/formation assays, imaging
The role of in vivo modulation of mechanical signals
In this project we will evaluate the effects of hyper or hypo-mechanical loading of cartilage chick limb in ovo model system to identify expression of factors that regulate endochondral ossification (EO). Eggs will be incubated until E10 and then tibiotarsi will be dissected and cultured in vitro in the presence of different factors to modulate EO. These factors will be NF-ĸB and mTOR activators and inhibitors. In a parallel experiment eggs will be incubated until E18 in the same conditions and with the presence of a paralysing agent, then legs will be collected for histology and µCT.
Techniques utilized: Embryonic limb organ culture, chick embryo model systems, imaging
The role of FSTL3 during male reproductive ageing
According with The U.S. Fish and Wildlife Service, the number of endanger species listed in the “Endangered Species Act” has increased from 200 in 1975 to nearly 1500 in 2015. During the same period of time, endangered mammalian species have increased from 100 to nearly 300. This is not only due to wildlife crime but also because of overuse of natural resources, human activity and climate change. Sexual reproduction is the mechanism by which mammals ensure the continuity of their existence on the face of the earth. During ageing, mammalian reproductive system declines its efficiency faster than any other system in the body, narrowing the time frame in which animals could reproduce. Previous work in our laboratory have shown that global deletion of FSTL3, a glycoprotein that exert inhibitory binding of activin, results in an 8-fold increase of spermatozoa production in mice at advanced age (22-month-old) compared to their wild-type counterpart. The aim of this project is to determine where in the different stages of spermatogenesis FSTL3 deletion triggers the over production of spermatozoa. Also to generate hints on which could be the molecular pathways by which FSTL3 deletion leads to the increase of spermatozoa production. The completion of this two aims will increase our understanding of mammalian male reproductive ageing and also will help to elucidate whether or not FSTL3 is a good molecular target to prolong male reproductive lifespan.
Techniques utilized: Mouse models Cre/lox system, Immunohistochemistry, Spermiogram , mRNA Seq analysis
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).
|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|