About us
The lab's research area, our values, and where our research happens.
Our research focus
The Twelvetrees Lab was established in April 2017 at the Sheffield Institute for Translational Neuroscience at the University of Sheffield. We aim to understand the role of microtubules and their motor proteins in neuronal health and disease.
Neurons form complex extended cellular structures; for example motor neurons have cell bodies in the spinal cord whilst extending axons down to the muscles of the hands and feet. Dendritic trees are also highly branched and spatially specialised structures. These morphological specialisations of neurons are essential to their function, but also hugely challenging as the majority of newly synthesised protein is made in the cell body and then actively transported to its site of use, up to 1 meter away. In addition, retrograde transport back to the cell body is required to remove ageing proteins and organelles from the distal neurites for degradation, as well as to relay neurotrophic survival signals back to the cell body.
Almost all the long distance transport events in neurons fall under the label of ‘microtubule mediated transport’. This label masks a complex set of co-dependent intracellular trafficking events of a huge array of cargos critical for maintaining neuronal homeostasis. There is now a large body of evidence demonstrating deficits in transport in multiple unrelated adult-onset neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, as well as motor neuron diseases such as amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegias (HSPs). In addition, deficits are frequently found as an early event in disease models.
Despite the complexity of transport as a cellular process, almost all long distance neuronal transport events are carried out by the same set of machinery: microtubules and microtubule motor proteins (dynein and kinesins). This commonality means that therapeutic strategies aimed at this system could have broad applicability to many diseases. However, there are many fundamental unknowns in our understanding of how motor proteins function as part of regulated systems within neurons, and this is a roadblock in developing treatments.
The primary aim of our research is to understand the molecular mechanisms that govern a particular type of axonal transport termed slow axonal transport, and ask how these are altered in disease models. We do this by applying the tools of biochemistry and biophysics within neuronal cells. By conducting this research within SITraN we aim to maximise the translation of our work for drug discovery.
Our Values
Our lab values centre around creativity, integrity and respect. In practice these are embodied by different habits we use as a group to carry out our projects.
Creativity
We want to embody creativity in how we approach our scientific questions, experimental design & solve problems at the bench. This is the essential characteristic of creating new knowledge and we let it find expression in our work wherever we can. It also helps bring joy to the everyday parts of the job.
Integrity
We set our bar high for scientific integrity. To ensure we meet our own standards our aim is to make the products of our research as open and as accessible as possible. To help us achieve openness and make our research accessible to the broadest scientific audience we aim to deposit our data, plasmids and code when we release our manuscripts. We also work hard on our writing and data presentation standards to make sure our research can be understood by a broad scientific audience, from clinicians to biophysicists. Examples in practice include spending time developing data presentations and using colour blind friendly palettes.
At the bench, we work hard to maintain our sample integrity, working with care and diligence. Care in sample preparation is key to unlocking the technically demanding nature of our work.
Respect
Respect is really important to us. We respect each other, our samples and reagents, our resources and equipment. Perhaps most importantly we respect our time. We work hard to take care of each of these.
We value and respect everyone’s individuality and the unique creativity they bring to projects. This is embodied by giving everyone agency over their projects to shape the direction in way that fulfils their personal ambitions. We respect each others work with the knowledge that nobody’s experiments are more important than anyone else’s.
We respect and value our resources by working towards the sustainability and efficiency of our experiments. This means making sustainable choices when choosing equipment to purchases, taking care of equipment and resources, embracing automation, reducing our reliance on animal products, and making things reusable where possible.
We respect and value our own time and that of our co-workers by being organised and prepared. We schedule deadlines, we label and store reagents properly so they are easy to find, we keep the lab tidy so it’s easy to work. These are small things, but they make a big difference.
If the team is successful, everyone will be successful. We will always value teamwork & collaboration.
If this sounds like values that you could enjoy putting into practive, maybe you would like to join the team
The University of Sheffield
SITraN is part of the University of Sheffield's Department of Neuroscience in the Faculty of Medicine, Dentistry and Health. Neuroscience is a key strength of the University which extends far beyond the department in a cross faculty Neuroscience network.
The University of Sheffield is a research intensive university: a member of the Russell group; ranked in the top 5 UK institutions for Biological Research (REF 2014); a world top 100 university.
Perhaps even more importantly, The University of Sheffield is a fantastic place to learn and work: voted #1 in the Russell Group for student experience (THE); ranked at number 25 in the Sunday Times 100 Best Not-For-Profit Organisations to Work For 2017 (the only university to be featured in this ranking of Britain's happiest and most motivated workforces); ranked in the Stonewall top 100 workplaces for LGBT equality for 4 years running; the Medical School currently holds a Silver Athena SWAN award.
In the lab we aim to model Sheffield's principles and provide a supportive, dynamic and exciting environment in which to work.
The City of Sheffield
Sheffield is home to half a million people. Once you arrive you'll have the chance to get to know what a brilliant, fun and quirky place to live and work it is, all on the doorstep of the Peak District National Park (as you can probably tell from the gallery, this is one of the things we love most about living here). Variously known as The Steel City, England's largest village, The Outdoor City, as well as beer-capital of the World, Sheffield is absolutely jam-packed with arts, culture, restaurants and bars. Here are some of our favourite city guides: