Tag Archives: University College of Dublin

‘Llam’ me lend you some antibodies—antibody particles extracted from camels and llamas

Sometimes the urge for wordplay overwhelms me as it did this morning (June 12, 2014) when I saw llamas mentioned in a news item. For anyone unfamiliar with how Canadian English (and I can safely include American English here but am not sure about any other Englishes) is spoken, we leave out consonants in some phrases. For example, ‘let me’ becomes ‘lemme’, which when you’re playing with ‘llama,’ becomes ‘llam’me. As for the verb ‘lend’, I used it for its alliterative quality and used more accurate verb ‘extracted’ later in the headline.

Getting on to the antibodies and the camels and llamas, here’s more from a June 12, 2014 news item on Nanowerk (Note: A link has been removed),

The use of nanoparticles in cancer research is considered as a promising approach in detecting and fighting tumour cells. The method has, however, often failed because the human immune system recognizes the particles as foreign objects and rejects them before they can fulfil their function. Researchers at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and at University College Dublin [UCD[ in Ireland have, along with other partners, developed nanoparticles that not only bypass the body’s defence system, but also find their way to the diseased cells (“Diagnostic nanoparticle targeting of the EGF-receptor in complex biological conditions using single-domain antibodies”). This procedure uses fragments from a particular type of antibody that only occurs in camels and llamas. The small particles were even successful under conditions which are very similar to the situation within potential patients’ bodies.

A June 12, 2014 HZDR press release, which originated the news item, supplies a quote from one of the researchers where he explains the problems he and his colleagues were attempting to address,

Describing the current state of research, Dr. Kristof Zarschler of the Helmholtz Virtual Institute NanoTracking at the HZDR explains, “At the moment we must overcome three challenges. First, we need to produce the smallest possible nanoparticles. We then need to modify their surface in a way that the proteins in the human bodies do not envelop them, which would thus render them ineffective. In order to ensure, that the particles do their job, we must also somehow program them to find the diseased cells.” Therefore, the Dresden [HZDR is in Dresden] and Dublin researchers combined expertise to develop nanoparticles made of silicon dioxide with fragments of camel antibodies.

The press release and Zarschler go on to explain the advantages of camel and llama antibodies,

In contrast to conventional antibodies, which consist of two light and two heavy protein chains, those taken from camels and llamas are less complex and are made up of only two heavy chains. “Due to this simplified structure, they are easier to produce than normal antibodies,” explains Zarschler. “We also only need one particular fragment – the portion of the molecule that binds to certain cancer cells – which makes the production of much smaller nanoparticles possible.” By modifying the surface of the nanoparticle, it also gets more difficult for the immune system to recognize the foreign material, which allows the nanoparticles to actually reach their target.

The ultra-small particles should then detect the so-called epidermal growth factor receptor (EGFR) in the human body. In various types of tumours, this molecule is overexpressed and/or exists in a mutated form, which allows the cells to grow and multiply uncontrollably. The Dresden researchers could demonstrate in experiments that nanoparticles that have been combined with the camel antibody fragments can more firmly bind to the cancer cells. “The EGFR is a virtual lock to which our antibody fits like a key,” explains Zarschler.

Most exciting are the experiments the researchers performed with human blood (from the press release),

They even obtained the same results in experiments involving human blood serum – a biologically relevant environment the scientists point out: “This means that we carried out the tests under conditions that are very similar to the reality of the human body,” explains Dr. Holger Stephan, who leads the project. “The problem with many current studies is that artificial conditions are chosen where no disruptive factors exist. While this provides good results, it is ultimately useless because the nanoparticles fail finally in experiments conducted under more complex conditions. In our case, we could at least reduce this error source.”

There are no immediate plans for clinical trials according to the press release,

However, more time is required before the nanoparticles can be utilized in diagnosing human tumours. “The successful tests have brought us one step further,” explains Stephan. “The road, however, to its clinical use is long.” The next aim is to reduce the size of the nanoparticles, which are now approximately fifty nanometres in diameter, to less than ten nanometres. “That would be optimal,” according to Zarschler. “Then they would only remain in the human body for a short period – just long enough to detect the tumour.”

Here’s a link to and a citation for the paper,

Diagnostic nanoparticle targeting of the EGF-receptor in complex biological conditions using single-domain antibodies by K. Zarschler, K. Prapainop, E. Mahon, L. Rocks,  M. Bramini, P. M. Kelly, H. Stephan, and K. A. Dawson. Nanoscale, 2014,6, 6046-6056 DOI: 10.1039/C4NR00595C
First published online 16 Apr 2014

This paper is in an open access journal.

The researchers have provided an illustration of the new antibody particles,

 Title Bild Nanopartikel Copyright 	CBNI, UCD


Title Bild Nanopartikel
With help of proteins, nanoparticles can be produced, which bind specifically to cancer cells, thus making it possible to detect tumours. Copyright CBNI, UCD

Nanopore instruments, femtomolar concentrations, Ireland, and New Zealand

It was the word femtomolar that did it for me. While I have somehow managed to conceptualize the nanoscale, the other scales (pico, femto, atto, zetto, and yocto) continue to  elude me. If my experience with the ‘nanoscale ‘ is any guide, the only solution will be to find as much information as I can on these other ones and immerse myself in them. With that said, here’s more from the July 19, 2012 Izon press release,

Researchers at the Lee Bionanosciences Laboratory at UCD [University College Dublin] School of Chemistry and Chemical Biology in Dublin have demonstrated the detection and measurement of biological analytes down to femtomolar concentration levels using an off the shelf qNano instrument. This ultra low level biodetection capability has implications for biomedical research and clinical development as trace amounts of a biological substance in a sample can now be detected amd quantfied using standard commercially available equipment.

Platt [Dr Mark Platt] and colleagues’ [Professor Gil Lee and Dr Geoff Willmott] method for femtomolar-level detection uses magnetic particle systems and can be applied to any biological particle or protein for which specific aptamers or antibodies exist. Resistive pulse sensing, the underlying technology of the qNano [Izon product], was used to monitor individual and aggregated rod-shaped nanoparticles as they move through tunable pores in elastomeric membranes.

Dr Platt says, “The strength of using the qNano is the ability to interrogate individual particles through a nanopore. This allowed us to establish a very sensitive measurement of concentration because we could detect the interactions occurring down to individual particle level.

”The unique and technically innovative approach of the authors was to detect a molecule’s presence by a process that results in end on end or side by side aggregation of rod shaped nickel-gold particles. The rods were designed so that the aptamers could be attached to one end only.

“By comparing particles of similar dimensions we demonstrated that the resistive pulse signal is fundamentally different for rod and sphere-shaped particles, and for rod shaped particles of different lengths. We could exploit these differences in a new agglutina¬tion assay to achieve these low detection levels,” says Dr Platt.

In the agglutination assay particles with a particular aspect ratio can be distinguished by two measurements: the measured drop in current as particles traverse the pore (∆ip), which reveals the particle’s size; and the full width at half maximum (FWHM) duration of the resistive pulse, which relates to the particle’s speed and length. Limits of detection down to femtomolar levels were thus able to be demonstrated.

I’m a little unclear as to what qNano actually is. I did find this description on the qNano product page,

qNano uses unique nanopore-based detection to enable the physical properties of a wide range of particle types to be measured with unsurpassed accuracy.

Detailed Multi-Parameter Analysis.

Particle-by-particle measurement through qNano enables detailed determination of:

Nanopore-based detection allows thousands of particles to be measured individually, providing far greater detail and accuracy than light-based techniques.

Applications & Particle Types

A wide range of biological and synthetic particle types, spanning 50 nm – 10 μm, can be measured, across a broad range of research fields.

qNano Package

qNano is sold as a full system ready for use including the base instrument, variable pressure module, fluid cell and a starter kit of nanopores, buffer solution and standard particle sets.

Here’s what the product looks like,

qNano (from the Izon website)

As for what this all might mean to those of us who exist at the macroscale (from the Izon press release),

Izon Science will continue to work with Dr Platt at Loughborough, and with University College Dublin and various customers to develop a series of diagnostic kits that can be used with the qNano to identify and measure biomolecules, viruses, and microvesicles.“This is a real milestone for Izon’s technology as being able to measure biomolecules down to these extremely low levels opens up new bio-analysis options for researchers. 10 femtomolar was achieved, which is the equivalent dilution to 1 gram in 3.3 billion litres, or 1 gram in 1300 Olympic sized swimming pools,” says Hans van der Voorn, Executive Chairman of Izon Science.

For those interested in finding out about nanopores, these were mentioned in my July 18, 2012 posting while aptamers were discussed in my interview (Oct. 25, 2011 posting) with Dr. Maria DeRosa who researches them in her Carleton University laboratory (Ottawa, Canada).

Future of Film & Video event being livestreamed from Dublin’s Science Gallery July 13, 2012

As I’ve noted previously (my April 29, 2011 posting) Dublin is celebrating itself as a ‘City of Science’ this year. As part of the festivities (e.g. the Euroscience Open Forum [ESOF} meetings are now taking place in Dublin), the Future of Film & Video at the Science Gallery will be livestreamed on Friday, July 13, 2012 from 1800 to 1930 hours (10 am – 11:30 am PST), from the event page,

Join Academy award winners Anil Kokaram and Simon Robinson, and BAFTA award winner Mark Jacobs as they discuss the future of film and video, from today’s cutting-edge 3D tech, to tomorrow’s innovations being imagined in labs across the world. You’ll never look at a screen the same way as these visionaries show that in the film and video industry you should expect the unexpected.

This event is part of the UCD Imagine Science Film Festival, and is part of Dublin City of Science. We are grateful for the support of Google Dublin, the Chrome-Media Group at Google, Mountain View, the Sigmedia Group in the Engineering Dept, Trinity College Dublin and also Science Foundation Ireland.”

Simon Robinson

Academy Award winner, Simon Robinson is a Founder and the Chief Scientist of The Foundry, one of the most well recognised names in the creation of visual effects software. His technology has touched most of the blockbusters that reach our screens today e.g. Oscar Winning titles Hugo, Rango and effects laden works such as The Matrix, The Lord of the Rings and Avatar. In 2007 he was awarded a SciTech Academy Award for his influence on motion picture technology and in 2010 he was ranked in the top 100 most creative people in business in the fast Company’s annual ranking. His company has made the Sunday Times tech track top 100 list for two years in a row. The Foundry now numbers over 100 employees and speaking to the FT recently Simon is quoted as saying , “We never wanted to grow beyond six staff. We never thought we would sell it. We never thought we would buy it back. We are often wrong.”

Mark Jacobs

Mark Jacobs is a BAFTA award winning Producer/Director with a unique track record in innovation. His extensive experience of more than 25 years in broadcasting, with the BBC and other organisations, ranges from traditional programme making and commissioning, to delivering cutting edge innovation. Mark pioneered some of the first applications of 3D animation for both the BBC and Discovery and in 2000 he joined the BBC’s R&D arm to help pioneer new ways of using multimedia content.  Mark has recently produced a 40 minute, multi-screen interactive film for the Natural History Museum with David Attenborough and led the BBC’s series of natural history documentary trials for stereo 3D production. He has a BAFTA for Interactive TV/ Mobile and introduced some of the first tests in computer graphics and augmented reality into the BBC. He has produced many award winning films for BBC series, ranging from Wildlife On One and Supersense to landmark series on the natural history of Polynesia and Central America and also a programme on the Dingle Dolphin!

Anil Kokaram

Academy award winner, Anil Kokaram is a Professor at Trinity College Dublin with a long history in developing new technologies for digital video processing and particularly in the art of making old movies look like new. He started a company called GreenParrotPictures in 2004 which specialised in translating cinematic effects tools into the semi-professional and consumer space. In 2007 Anil was awarded a SciTech Academy award for his work in developing motion estimation technology for the cinema industry in collaboration with Simon Robinson.  GreenParrotPictures was acquired by Google in 2011 and Anil now heads a team of engineers in the Chrome Media Group in the Googleplex, Mountain View, California developing new video tools for Chrome and YouTube.  He continues to collaborate with his research group www.sigmedia.tv in Trinity College Dublin.

Location:

Paccar Theatre

Admission:

Free – prebooking essential  [go to event page to prebook]

I’m hoping this will be focussed on something other than the future of 3D technology.