As mentioned in one of my previous posts [click here] this summer I am undertaking a biomedical research project in collaboration with the Nuffield foundation on the topic of: “The role of Tenascin C in tendinopathy”. My main goal for tackling on this ‘challenge’ (I guess) was to engage in some real life science and to better myself in preparation for university. Though I am fortunate to attend a school which go out of their way to provide specialised scientific equipment, I had never experienced university style labs in (as the researchers I worked with called it) the big bad world. I realised that I took for granted the seemingly simple apparatuses such as autoclaves and centrifuges as some undergraduates haven’t even seen one in real life until university, never mind using them. I was overjoyed to leave the world of school bucket chemistry behind which solely consisted of school technicians tirelessly making up solutions only for us to haphazardly throw them all together to see the really tell-tale signs such as a colour change. No, I savoured every moment of making my own discoveries, never again shall I robotically repeat the same boring experiments to end up with a result I already knew.
My project was of particular relevance due to the fact that soft tissue disorders represent the third most common musculoskeletal condition in the UK (18 cases per 1000). These primarily affect tendons: this accounts for 30% of all musculoskeletal consultations with a general practitioner. The extracellular matrix molecule tenascin-C is highly expressed during embryonic development, tissue repair and in pathological situations such as chronic inflammation and cancer. Tenascin-C interacts with several other extracellular matrix molecules and cell-surface receptors, thus affecting tissue architecture, tissue resilience and cell responses. Inflammation is a critical and immediate response to tissue injury and infection. Pattern recognition receptors (PRRs) recognise both pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) and in response stimulate the expression of pro-inflammatory genes. The tenascin-c expression is induced at sites of inflammation, apparently regardless of the location or type of causative insult. The expression is observed upon both tissue injury, for example during incisional wounding and tendon rupture. Our laboratory has previously identified that the damage associated molecule, interleukin 33 is upregulated and released following tendon damage and is associated with subsequent collagen matrix changes. Little remains known about the pathophysiological mechanisms underlying the release and signalling of damage associated molecules in tendinopathy. Tendon biopsies obtained from normal (n=5) and diseased (n=5) patients will undergo immunohistochemical evaluation for the expression and localisation of Tenascin C. Additionally further normal and disease tendons will undergo enzymatic digestion to isolate human tenocytes. Subsequently, in vitro experiments will analyse the effect on inflammatory and matrix related pathways on the addition of Tenascin C in an attempt to understand the molecular mechanisms involved in tendon damage.
Looking back I feel like the most pressing issue for me throughout the project was patience. This may sound a bit odd but I spent a large portion of my day in the histology department which focused on the study of the microscopic structure of tissues. Now, wish to clarify that histology is not the following:
…but it does make students feel like this.
However, I must say most of my time was occupied by waiting with a timer for all the slides to go through the various dewaxing and dehydration stages. On a more positive note, I was able to speak to researchers who were very committed, ‘ Research is really my hobby, to be paid for your hobby is a great thing.’. He and another fellow enthusiast had started out a spin out company from the University who has encountered a break through and is currently undergoing clinical trials for a special type of microRNA which suppresses collagen 3 so that collagen 1 is able to do its magical work. During tendinopathy, collagen 1 level remains relatively stable whilst collagen 3 gets a bit mad and quickly repairs the damages tendon. However, most of the repair work by collagen 3 consists of scar tissue which is no longer able to perform the functions of a healthy tendon to the same extent. By being able to make full use of collagen 1, the tendon is able to regenerate to its original state and sometimes surpass its original state. They have now reached the clinical trial stage, firstly on horses at the vet school then humans, so far they have found the same results in horses and humans. As one of the researchers say, “I still can’t believe this is real, even though I’ve seen the results with my own eyes.” And with this exciting new discovery, I hope in future you will find yours as well.
Author – Jiangmin Hou
Jiangmin is a 5th year high school student currently studying five STEM subjects at Scottish Higher level-Mathematics, Physics, Biology, Computer Science and Chemistry. She is interested in pursuing a degree in Medicine after completion of Secondary Education.