Age, diabetes and having the two copies of the gene for apolipoprotein E 4 (APOE ε4) are just some of the factors that significantly increase the chance of developing Alzheimer’s disease later on in life. Associate Professor Carmela Matrone’s research group used stem cells generated from Alzheimer’s disease patients with the APOE ε4 gene to show that this genetic risk factor is connected to a deterioration of a relationship between two key proteins, sortilin-related receptor (SORL1) and amyloid precursor protein (APP) 1 .
Axol Bioscience Science Scholarship recipient, Nataly Martynyuk, is a PhD student at the Brain Repair Centre, Department of Clinical Neurosciences, University of Cambridge, UK. Her research focuses on the actions of alpha-chimaerins in mechanisms relevant to dendritic spine formation and neurodegeneration. Nataly has written a review on astrocytes as part of her scholarship application.
Axol Bioscience travel grant recipient, Marie Franquin attended Gordon Research Conference - Neurobiology of Brain Disorders 2016, which took place in Girona, Spain. Marie is a PhD student at the Centre for Research in Neuroscience, McGill University, Canada. Her research focuses on the role of TNF alpha on synaptic plasticity defects in neurodegenerative diseases. Marie shares her experience of the conference where she presented her research.
Axol Bioscience travel grant recipient, Abigail Robertson attended Frontiers in CardioVascular Biology 2016, which took place in Florence, Italy. Abigail is a PhD student at the Institute of Cardiovascular Sciences , University of Manchester, UK. Her research focuses on targeting the Hippo signalling pathway to enhance the therapeutic potential of iPSC-derived cardiomyocytes . Abigail shares her experience of the conference where she presented her research.
Our understanding of the central nervous system (CNS) has grown significantly in recent years. The advent of new technologies and products have enabled us to explore not only the molecular mechanisms involved in learning, development, memory formation, electrical conductivity and synaptic function but also the onset and deterioration of these systems in neurological disorders such as epilepsy, amyotrophic lateral sclerosis (ALS), Alzheimer’s, Huntington’s and Parkinson’s diseases as well as psychiatric conditions.
Epilepsy is one of the most common neurological disorders. The age of onset is typically early with potentially serious neurocognitive residuals apparent in later life. Symptoms can include recurring aggressive electrical activity, seizures, behavioural, neurological and cognitive difficulties, and may result in early death.
“It is truly amazing that a complex organism, formed through an extraordinary intricate process of morphogenesis, should be unable to perform the much simpler task of merely maintaining what already exists.”
For starters, my student Paul and I did some homework on our poster to ensure that it was audience appropriate; with Paul's help I made the message simple and clear enough to allow us to be able to explain the poster to anyone of any age and background. Angela then offered me another layer of challenge on top of the poster - designing a game for my research so that I can explain my work to our visitors at the conference. Once again I was not sure, what kind of game could I make for kids that would make my research fascinating to them? Angela's creative mind really made it easy on the D-day as I arrived with my poster! With her help, we created a little game with glitters and can of water and made a really cool experiment to help people understand the fundamentals about the brain and its barriers.
MicroRNAs are short noncoding 18-25 nucleotide long RNA which bind and inhibit mRNA. Currently, there are over 1000 known human microRNAs, and microRNAs control over 50% of mammalian protein coding genes. As more is learnt about the regulation and wide reaching function of microRNA, their importance in regulating cell pathways in homeostasis and disease are becoming more apparent. As with other tissues, microRNAs have been identified to play important roles in heart development, homeostasis, exercise induced hypertrophy, and disease. During development, several microRNA have been shown to be upregulated during specific points, such as miR-1, miR-133 and miR-15 which all play important roles in ventricular cardiomyocyte expansion. MicroRNA have also been found to play important roles in exercise induced changes in the heart, such as miR-222 which is upregulated during exercise and has also been found to be protective against ischemia reperfusion in the mouse. In both human and animal studies many microRNA have been shown to be regulated during disease in the heart, and in animal studies reversal of disease can be seen when these microRNA are reverted back to baseline levels. For example the cardiac specific miR-208a is upregulated during pathological cardiac hypertrophy in mice after thoracic aortic banding. When miR-208a knockout mice were banded there was no hypertrophy or fibrosis observed demonstrating that increased miR-208a leads to increased hypertrophy in the mouse heart after thoracic aortic banding.
We have now reached day 10 of our investigation into the suitability of Axol hyCCNs for studying axonal biology using microfluidic culture devices. Day 9 fell on a Sunday so we have cheated slightly and changed media on Day 10 instead (not recommended). Fortunately, the cells survived over the weekend without too much distress. Prior to today, we prepared the microfluidic culture device and began the culture of human cerebral cortical neuron with the expectation that the axons would pass through the microgroove within 2 weeks of plating the cells. During this culture period we have been exchanging media every 2 days while waiting for the axons to appear!
We have reached day 7 of our investigation into the suitability of Axol hyCCNs for studying axonal biology using microfluidic culture devices. Unfortunately, the major highlights at these point are changing media and checking cells under the microscope while we wait for the assay to come to fruition (a familiar scenario to those experienced in cell culture). Prior to today, we prepared the microfluidic culture device and began the culture of human cerebral cortical neuron with the expectation that the axons would pass through the microgroove within 2 weeks of plating the cells.
On day 5 of our investigation into the suitability of Axol hyCCNs for studying axonal biology using microfluidic culture devices, the major step is to exchange the medium! Previously, we prepared the microfluidic device and started culturing the human cerebral cortical neurons. The expectation is that the axons will pass through the microgroove in the microfluidic device within 2 weeks of plating the cells.
1. Rinse the cover glass several times with sterile dH2O in the tissue culture hood. Leave the cover glass in dH2O as you sterilize the microfluidic device. Then remove from water and allow the cover glass to air dry in the hood at the same time as the device.
We are hoping to show that Axol human cerebral cortical neurons can easily be adapted to grow in a microfluidic culture device allowing us to separate cell bodies from the extended axons and we will be blogging our progress along the way. This culturing method has many potential applications including investigating biochemical analysis of pure axonal fractions, studying axonal injury and studying axonal regeneration.
As a basic scientist performing research in a hospital many of my colleagues and people around me work every day to save people’s lives in a very direct way. I work on a protein involved in cellular pathways in disease and I often wonder whether what I am doing will ever have an impact on people in the medical field. But I love my job and believe that what we do as basic scientists for medicine is just as important and crucial for understanding and treatment of disease as our clinician colleagues. Our job is to answer fundamental questions about life and our surroundings, leading to an increase in information, knowledge and therapeutics available which can be used to help our society and improve our lives.
In many ways, getting a PhD is like running a marathon. A marathon with hurdles positioned at every mile mark to be precise. It is not a “pleasant” experience per se, but you will come out a finisher, which is pretty much the same thing as a winner in my book. Here is my story.
In what feels like a lifetime ago, I started my PhD journey with the hope of studying gene therapy. Unfortunately, due to funding issues, I was not able to join the lab of my choice. In fact, six rotations later, I found myself in an immunology lab that consists solely of my PI and me.