William Gan

Complement: Past, Present and Future?

by William Gan

(Image source: Pixabay)

The immune system, the body’s defense mechanism, is what protects us against pathogenic infections. In a nutshell, it is a complex network of specialized cells and proteins that interact with one another, generating unique signals to eliminate foreign pathogens. In the world of research, immunologists are the people that strive to unravel the secrets that lurk within the many different aspects of immunity.

One of these stories began in 1891, when Hans Ernst August Buchner discovered a blood serum factor responsible for killing bacteria, naming it ‘alexin’, later renamed as ‘complement’ by Paul Erlich at the turn of the 20th century. As part of the innate immune system, complement enhances the ability of antibodies and other immune cells to clear pathogens, also playing roles in inflammation and killing of microbes.

The complement system is simply a collection of small proteins, dispersed in blood plasma in their inactive forms like mines in a minefield, waiting to be triggered by immune complexes, foreign material, damaged cells, etc. All three activation pathways in this complex system lead to the generation of C3 convertase, a protease made up of other activated complement protein fragments, cleaving C3 to make C3a and C3b.

C3b covalently binds to pathogenic surfaces, marking a target to be eliminated by phagocytes. Most importantly, it associates with its ‘maker’ to form C5 convertase that drives the terminal pathway, ultimately creating a membrane attack complex that literally rips a hole on a targeted membrane! In this chaotic cascade of protein-protein interactions, regulatory proteins exist to inactivate complement and prevent ‘unwanted explosions’, much like a dedicated bomb defusal squad.

When cells go boom! (Image source: Pixabay)

But imagine if these ‘bombs’ could somehow go rogue, perhaps through mutations that result in an altered protein function, or autoantibodies against regulatory proteins that tip the balance of complement control. The involvement of complement is the reason behind complications such as age-related macular degeneration, atypical haemolytic uraemic syndrome (aHUS) and especially paroxysmal nocturnal haemoglobinuria (PNH), characterised by complement-mediated destruction of red blood cells!

A major breakthrough in complement therapeutics came in 2007, with the release of eculizumab (Soliris), a terminal pathway inhibitor that proved to be effective in treating aHUS and PNH. However, drawbacks such as high costs and risk of meningococcal infections presents limitations to treatment but paves the way for next generation drugs like ravalizumab. C1 esterase inhibitors ie. Cinryze, Berinert and Ruconest, function to completely switch off complement and are currently used to treat hereditary angioedema.

The therapeutic landscape is constantly changing with the many possible innovations to improve future therapies ie. alternate drug administration routes, physiological barrier crossings, etc. But in the end, complement-mediated diseases constantly beg the question of the level of inhibition required, raising much interest as an ideal therapeutic choice. By modulating and reducing complement activity rather than turning it off, homeostasis could be restored thus treating disease while simultaneously maintaining the role of complement in immune defense!


Inspired by my final year research project and this simple, easy-to-understand video on complement:

Compendium of current complement therapeutics. (Newcastle researchers involved!) –

William Gan

The marvels of Life

by William Gan

As part of my undergraduate course, I’ve just recently been given the opportunity to visit the Life Science Centre, a prize-winning educational facility cum tourist attraction located in Times Square, Newcastle. The Life Science Centre is part of the Centre of Life, one of the projects funded by the Millennium Commission as a registered charitable trust. It is an internationally acclaimed self-funding ‘science village’ that also houses research laboratories, biotechnology companies, and National Health Service (NHS) clinics.

Centre for Life logo: If you look closely, the F actually resembles a duplicated chromosome!

Walking into the centre, it felt as if I was entering a large indoor theme park as the vibrant colours that decorate the exhibits come into full view. Fortunately, visitors are strongly encouraged to unleash their child-like instincts to wander and explore the various sections. Hence, it’s a well-known hotspot for schools to organise trips for young students to expose them to the world of science!

One of the permanent exhibitions, the Curiosity Zone, presents a range of interesting sections that includes spinning turntables, interactive walls and air-suspended beach balls, encouraging visitors to experiment through trial and error and have fun despite the absence of scientific content. It also features a ‘making space’ where younger ones can be armed with glue guns and cardboard amongst other materials to exercise their imagination and to get some hands-on action.

Noel Jackson, Head of Education at Centre for Life, says: “We want to break the stereotype that science isn’t all head knowledge, but more of the entire learning process that one experiences in discovering something.”

In the Experiment Zone, participants will be able to take part in actual experiments using real chemicals under supervision while donning lab coats. By creating opportunities for families to experience scientific discovery together, parents can foster the sense of scientific involvement in their children. The Brain Zone on the other hand explores how different disciplines can come together to study the mind. Optical illusions and other interactive tools are joined alongside relevant scientific content in presenting the inner workings of the mind.

Experiment Zone: Well-equipped lab stations with instructive digital panels for the budding scientist!

The Science Theatre is where the audience can experience the ‘artsy’ side of science, it’s without a doubt my most favourite section in the centre. Set in a dome-shaped enclosure with a dimly lit stage and rows of cushioned red seats, Science Explainers will tell a story while exploring a scientific topic with the use of live interactions and demonstrations. Shows are filled with visual wow factors ranging from gorgeous chemistry to fiery bubbles that may seem like pure magic. I personally feel that this concept is a great way to present science in an entertaining way especially towards a younger generation.

“By blurring the boundaries between science and arts, we hope that our audience can learn to watch closely, be curious and to ask questions, and at the same time see the beauty in science,” says Elin Roberts, Head of Public Engagement at Life Science Centre.

In the planetarium, visitors can experience an immersive, virtual tour of the night sky as well as view the solar system in high definition. While the audience are seated in comfy chairs, the planetarium presenters will describe exciting space endeavours while journeying through the cosmos! Speaking of space, special events are also available for adults or ‘big kids’ with the most upcoming one including discussions on the myth of a cheesy moon and lunar space missions, accompanied by a cheese and wine tasting session.

Mr Jackson further explains: “Parents in general play a key role in shaping their child’s perspectives on life, finding joy and genuine enthusiasm in a field like science can influence the younger generation to also find their own passion in life.”

Want to learn more? Check out Newcastle’s Centre for Life on their website, or visit them in person soon!