Feature in leading pharmaceutical technology journal

Research from academics in the Schools of Pharmacy and Life Sciences is the focus of a feature in Innovations in Pharmaceutical Technology.

​Dr Enrico Ferrari from the School of Life Sciences, who specialises in assembling proteins, and Dr Ishwar Singh from the School of Pharmacy, who has expertise on DNA-binding molecules, are part of an international project which aims to drastically improve cancer diagnostics and treatment options.

They will be creating a diagnostic ‘nanodecoder’, which will consist of self-assembled DNA and protein nanostructures, which will greatly advance biomarker detection and provide accurate molecular characterisation enabling more detailed evaluation of how diseased tissues respond to therapies.

Dr Singh and Dr Driton Vllasaliu are also carrying out research into how medicinal ‘biologics’ can be delivered to diseased cells​, with the aim of creating new treatments for prostate cancer, Multiple Sclerosis and cystic fibrosis.

Read the feature in Innovations in Pharmaceutical Technology.

The article is taken from Innovations in Pharmaceutical Technology, March 2015 issue, pages 52-54. © Samedan Ltd​

‘Designer’ nanodevice could improve cancer treatments

Cancer diagnostics and treatment options could be drastically improved with the creation of a ‘designer’ nanodevice being developed by researchers from the UK, Italy, the US and Argentina.

The diagnostic ‘nanodecoder’, which will consist of self-assembled DNA and protein nanostructures, will greatly advance biomarker detection and provide accurate molecular characterisation enabling more detailed evaluation of how diseased tissues respond to therapies. A biomarker, or biological marker, refers to a measurable indicator of some biological state or condition. One example of a commonly used biomarker in medicine is prostate-specific antigen (PSA). This marker can be measured as a proxy of prostate size with rapid changes potentially indicating cancer.

The four-year ‘Immuno-NanoDecoder’ project involves lead partner University of Rome Tor Vergata, Italy; together with University of Lincoln, UK; Hospital of Udine, Italy; Temple University, Philadelphia, Pennsylvania; and University of Buenos Aires, Argentina.

The project’s long-term goal is to develop a molecular nanodevice for imaging of biomarkers in tissue samples and cells. It will initially help to accurately characterise skin cancers and glycogenosis type II (where the body cannot get rid of glycogen from the muscles), being especially useful to assess in vitro the effectiveness of experimental therapies.

It is funded with a 441,000 Euro grant from the Marie Skłodowska-Curie Research and Innovation Staff Exchange (RISE) programme.

The University of Lincoln team will be responsible for engineering and synthesising a key component of the nanodevice: a two way molecular connector to bind the protein part to the DNA scaffold.

Lincoln’s involvement will be led by Dr Enrico Ferrari from the School of Life Sciences, who specialises in assembling proteins, and Dr Ishwar Singh from the School of Pharmacy, who has expertise on DNA-binding molecules, have a number of hybrid molecular devices in mind.

Dr Ferrari, whose previous research led to the creation of a new bio-therapeutic molecule that could be used to treat neurological disorders, said: “Once a cancer has been diagnosed the next stage is to try various treatment methods, but it is often difficult to understand the specific effect of treatment. This nanodecoder is the perfect tool to be able to both diagnose cancer accurately and record therapeutic effects.

“Our hybrid nanodevice is an artificial device made out of DNA and protein. Molecules arranged in a very specific way can perform a function – this is what we are trying to achieve, in an artificial way. It’s like DNA origami; it’s possible to engineer different shaped molecules but we want to engineer molecules that also have a function. After this project, we will be in a position to claim we have a very well defined expertise to make hybrid molecular devices.”

Research will take place in the Peptide Suite within the University of Lincoln’s new state-of-the-art Joseph Banks Laboratories. The Suite was created following funding from The Royal Society and the University’s Research Investment Fund.

Using a high-resolution method called Atomic Force Microscopy the team will be able to look closely at the assembled nanodevice.

Dr Singh, whose research specialisms include antimicrobials, ‘biologics’ and DNA diagnostics, said: “Each nanodevice will be coupled to a specific molecular probe, such as an antibody, peptide, or protein that uniquely recognise disease biomarkers. The coupling will allow the nanodecoder to detect biomarker presence and distribution in cells and tissues using optical fluorescence microscopy – in other words making them shine. Different biomarkers can indicate whether the disease is in remission or where it may have spread. From this set of markers doctors can understand what the next step in the treatment process should be. The number of biomarkers that can be detected will be essentially unlimited and therefore the nanodecoder could serve as a platform to diagnose other cancers and diseases. This project is an excellent vehicle to test our molecular tools and understand the potential of our first hybrid device.”

The nanodecoder, once created, will be trialled at the University of Buenos Aires, Argentina and at the Hospital of Udine, Italy. Complementary research programs, ranging from nanotechnology to molecular medicine and pathology, will support the project.

Lincoln academic presents to politicians

Research by a University of Lincoln academic was chosen to appear in Parliament.

 Dr Enrico Ferrari, a senior lecturer in the School of Life Sciences, presented his research to a range of politicians and a panel of expert judges, as part of SET for Britain on Monday, 18 March.

The only national event of its kind, SET for Britain aims to encourage, support and promote Britain’s early-stage and early-career research scientists, engineers and technologists.

Dr Ferrari’s research focusses on the toxin clostridium botulinum, commonly known as Botox, and expanding its potential as a prodigious drug that could be used for the treatment of disorders such as cerebral palsy, Parkinson’s and chronic migraine.

The technique of refining the Botox protein has been patented by the Medical Research Council and it is thought to have a potential impact not only on the design of new therapeutics but also on protein immobilization and nanotechnology.

Dr Ferrari was entered into the Biological and Biomedical Sciences session of the event.

He said: “It is a great honour to have been shortlisted from hundreds of other applicants and I hope my research will have a great impact on managing chronic pain conditions.”

Andrew Miller MP, Chairman of the Parliamentary and Scientific Committee, said, “This annual competition is an important date in the parliamentary calendar because it gives MPs an opportunity to speak to a wide range of the country’s best young researchers. These early career scientists are the architects of our future and SET for Britain is politicians’ best opportunity to meet them and understand their work.”

John Pierce, Chief Bioscientist at BP, sponsors of the Biological and Biomedical Sciences Gold award, said: “BP has supported SET for Britain for several years now and we continue to be impressed by the ingenuity and dedication of the UK’s young scientists. As a biologist, I am delighted that BP is sponsoring this particular award – traditionally engineering, physics, geology and chemistry have been the backbones of energy production, but we are increasingly seeing how biology impacts that. As a major UK recruiter and investor in research and development, we believe that we need to nurture the best technical talent to meet the world’s challenges.”

Beyond Botox: natural born killer or medical miracle?

Botox is best known for its use in cosmetic procedures, but this potent neurotoxin could be transformed into an extraordinary drug to treat a raft of debilitating conditions, a leading scientist will tell an audience at the University of Lincoln.

Synthesised by clostridium botulinum, Botox is the most deadly poison known to man, however, in tiny doses it is widely used as an effective anti-aging treatment. In injection form the toxin blocks the signals that tell muscles to contract, reducing the appearance of wrinkles.

Now scientists are working to expand the toxin’s potential as a prodigious drug that could be used for the treatment of disorders such as cerebral palsy, Parkinson’s and chronic migraine.

A scientist from the University of Lincoln (UK), who is working on refining the botox protein, will talk about its use in treating a broad range of neurological disorders in a free public lecture on 19th March, 2013.

Dr Enrico Ferrari, from the University’s School of Life Sciences, will also reveal the future avenues for turning this natural born killer into a therapeutic drug.

He said: “Many painkillers relieve pain temporarily and have various side effects. The selling point of this molecule is that the pain relief could last up to seven months, in a similar way that Botox injections last for several months. Engineering this kind of toxin has many uses and would be a major improvement in the quality of life for those people who suffer from chronic pain.”

Dr Ferrari joined the University in October 2012 after spending three years working with a group at the Medical Research Council’s Laboratory of Molecular Biology in Cambridge.

Led by Professor Bazbek Davletov, the team developed a new way of joining and rebuilding elements of the clostridium botulinum neurotoxin in a way that eliminated the unwanted toxic effects. In its natural state 150 nanograms would be enough to kill a person.

Dr Ferrari said: “The re-engineered toxin has very similar characteristics so is still able to block neurotransmission release, but the paralytic effect is a lot less because we have discovered a way to impede the toxin from reaching the muscles.”

The lecture entitled Beyond Botox: molecular engineering and the design of new therapeutics takes place at 6pm on Tuesday, 19th March at the University of Lincoln’s EMMTEC auditorium. Registration starts at 5.30pm.

This talk is part of the University’s LincolnAcademy series of free public events. Places should be booked in advance by calling 01522 837100 or e-mailing events@lincoln.ac.uk