It's a Small World: Nanotechnology meets Biology and Medicine

Professor Paula Mendes, Professor of Advanced Materials and Nanotechnology delivered her inaugrual lecture in January 2015.

 

There are very few people who can say their work is likely both to save millions of lives and create millions of lives (while also saving billions of pounds).

Professor Paula Mendes is one of them.

Her world-leading research is at the smallest scale, but its impact will almost certainly be huge.

Bringing together nanotechnology with biology and medicine, Paula is now within touching distance of being able to significantly improve the detection and treatment of infertility caused by low-quality sperm, and to diagnose diseases such as prostate cancer that are currently impossible to spot at an early stage, when the chance of long-term survival is highest.

With more than £2 million of funding from the EPSRC and ERC, the Portuguese-born Professor of Advanced Materials and Nanotechnology and her 15-strong research team may be as little as five years away from bringing new, efficient and cost-effective diagnostic tests out of the lab and into the clinic. Paula explains:

Our vision is to open an untravelled path in the successful diagnosis of many devastating human diseases, such as cancer, cardiovascular and neurodegenerative diseases 

Paula started her academic career as a traditional chemical engineer (her PhD was in high-intensity paper drying processes), but in 2002 the ‘buzz’ surrounding the newly emerging area of nanotechnology piqued her interest.

‘The area I chose for my PhD was a highly developed field already and I couldn’t see myself creating the impact I wanted to create,’ she recalls. ‘At the same time, there was this buzz about nanotechnology: here was something new that offered a lot of opportunities to make a difference.

‘Nature has perfected the art of biology at the nanoscale. Bio-nanotechnology is a natural marriage: nanotechnology allows a good interface with biology because they work at the same scale. It enables a new approach to measure, understand and control biological systems. We want to measure, for example, biomarkers, which are nano entities, so we need to get to the same level to detect them.’

Paula and her research team develop smarter biological interfaces by using switchable biological surfaces. ‘We are able to immobilise biomolecules (peptides) on a surface: they will just sit there. We can then create dynamic behaviour – exposing and concealing bioactive groups on demand, using an electrical potential.’

Creating dynamic behaviour enables scientists to mimic what is going on in the biological world – for instance, cells respond to dynamic cues.

One of Paula’s main areas of research is to understand more about sperm quality and dysfunction; in particular how sperm works and responds to signals in the female reproductive tract, which is central to the regulation of sperm activity. Working with Dr Jackson Kirkman-Brown, Science Lead at Birmingham Women's Fertility Centre, and Dr Steve Publicover in Biosciences, the researchers use nanotechnology to expose the female sex hormone progesterone in real time, allowing them to follow the calcium signalling and tail motility.

At present, says Paula, there isn’t a technology that can be used to accurately inform a clinician about sperm quality. The technology she is developing will not only help diagnose sperm dysfunction, it will also help clinicians pick the best fertility treatment – and so create life.

The current success rate of intra-cytoplasmic sperm injection (ICSI) – where the embryologist selects a single sperm to be injected directly into an egg, instead of fertilisation taking place in a dish where many sperm are placed near an egg – is less than 30 per cent and one of the reasons it’s so low is because of the quality of the sperm.


‘In the 22 years since ICSI was developed, there has been almost no progress in obtaining a robust, clinically significant and cost-effective tool for determining the selection of the best spermatozoon (motile sperm cell); but by being able to follow the calcium signalling in sperm in real time, we can pick the most functional cell (when there are not many sperm to choose from). Not only does it make fertility treatment more likely to work, it may also result in a pregnancy more quickly, which saves money.’

Saving lives is the other main area of Paula’s work: Detection of some diseases is notoriously difficult; the only available tests for prostate cancer, for example, show up false-positive results in 50 per cent of cases.

‘The current detection technique for diagnosis of prostate cancer is based on antibodies,’ says Paula, ‘but antibodies are not providing an accurate diagnosis. This is because most of the biomarkers for cancer and other diseases are glycoproteins – proteins with sugars attached – but the tests only detect quantities of glycoproteins; they can’t detect whether there is cancer present or not.’

If a man’s prostate-specific antigen (PSA) levels are high, he’s seen as being more likely to have prostate cancer, even though that might not be the case. A biopsy – which is costly for the NHS and unpleasant for the patient – is needed to confirm whether cancer is present.

‘PSA has different sugars: the sugar produced by normal cells is different to the sugar produced by cancer cells. So novel surface platforms for the detection of specific glycoprotein glycoforms enable us to differentiate between glycoproteins related to cancer and glycoprotein produced by a healthy individual – giving us a robust, reliable and cost-effective alternative to antibodies.’

Working with the Max Planck Institute in Germany as well as diagnostic companies, Paula and her team are ‘about five years away from being able to diagnose diseases such as prostate cancer and renal failure in multiple myeloma’.

It is, she acknowledges, ‘very exciting’ and she is ‘very proud’ of what she and her team have so far achieved. ‘As an academic, you want to be at the front of research.’

Today, that is exactly where Paula is – at the vanguard of bio-nanotechnology, and on the cusp of making a big difference.