̽��ֱ�� of Cambridge - Anna-Maria Pappa

Cell ‘membrane on a chip’ could speed up screening of drug candidates for COVID-19

sc604 — Mon, 06 Jul 2020 07:57:17 +0000

̽��ֱ��researchers, from the ̽��ֱ�� of Cambridge, Cornell ̽��ֱ�� and Stanford ̽��ֱ��, say their device could mimic any cell type--bacterial, human or even the tough cells walls of plants. Their research recently pivoted to how COVID-19 attacks human cell membranes and, more importantly, how it can be blocked.

̽��ֱ��devices have been formed on chips while preserving the orientation and functionality of the cell membrane and have been successfully used to monitor the activity of ion channels, a class of protein in human cells which are the target of more than 60% of approved pharmaceuticals. ̽��ֱ��results are published in two recent papers in Langmuir and ACS Nano.

Cell membranes play a central role in biological signalling, controlling everything from pain relief to infection by a virus, acting as the gatekeeper between a cell and the outside world. ̽��ֱ��team set out to create a sensor that preserves all of the critical aspects of a cell membrane—structure, fluidity, and control over ion movement—without the time-consuming steps needed to keep a cell alive.

̽��ֱ��device uses an electronic chip to measure any changes in an overlying membrane extracted from a cell, enabling the scientists to safely and easily understand how the cell interacts with the outside world.

̽��ֱ��device integrates cell membranes with conducting polymer electrodes and transistors. To generate the on-chip membranes, the Cornell team first optimised a process to produce membranes from live cells and then, working with the Cambridge team, coaxed them onto polymeric electrodes in a way that preserved all of their functionality. ̽��ֱ��hydrated conducting polymers provide a more ‘natural’ environment for cell membranes and allows robust monitoring of membrane function.

̽��ֱ��Stanford team optimised the polymeric electrodes for monitoring changes in the membranes. ̽��ֱ��device no longer relies on live cells that are often technically challenging to keep alive and require significant attention, and measurements can last over an extended time period.

“Because the membranes are produced from human cells, it’s like having a biopsy of that cell’s surface - we have all the material that would be present including proteins and lipids, but none of the challenges of using live cells,” said Dr Susan Daniel, associate professor of chemical and biomolecular engineering at Cornell and senior author of the ACS Langmuir paper.

“This type of screening is typically done by the pharmaceutical industry with live cells, but our device provides an easier alternative,” said Dr Róisín Owens from Cambridge’s Department of Chemical Engineering and Biotechnology, and senior author of the ACS Nano paper. “This method is compatible with high-throughput screening and would reduce the number of false positives making it through into the R&D pipeline.”

“ ̽��ֱ��device can be as small as the size of a human cell and easily fabricated in arrays, which allows us to perform multiple measurements at the same time,” said Dr Anna-Maria Pappa, also from Cambridge and joint first author on both papers.

To date, the aim of the research, supported by funding from the United States Defense Research Projects Agency (DARPA), has been to demonstrate how viruses such as influenza interact with cells. Now, DARPA has provided additional funding to test the device’s effectiveness in screening for potential drug candidates for COVID-19 in a safe and effective way.

Given the significant risks involved to researchers working on SARS-CoV-2, the virus which causes COVID-19, scientists on the project will focus on making virus membranes and fusing those with the chips. ̽��ֱ��virus membranes are identical to the SARS-CoV-2 membrane but don’t contain the viral nucleic acid. This way new drugs or antibodies to neutralise the virus spikes that are used to gain entry into the host cell can be identified. This work is expected to get underway on 1 August.

“With this device, we are not exposed to risky working environments for combating SARS-CoV-2. ̽��ֱ��device will speed up the screening of drug candidates and provide answers to questions about how this virus works,” said Dr Han-Yuan Liu, Cornell researcher and joint first author on both papers.

Future work will focus on scaling up production of the devices at Stanford and automating the integration of the membranes with the chips, leveraging the fluidics expertise from Stanford PI Juan Santiago who will join the team in August.

“This project has merged ideas and concepts from laboratories in the UK, California and New York, and shown a device that works reproducibly in all three sites. It is a great example of the power of integrating biology and materials science in addressing global problems,” said Stanford lead PI Professor Alberto Salleo.

References:
H-Y Liu et al. “Self-assembly of mammalian cell membranes on bioelectronic devices with functional transmembrane proteins.” ACS Langmuir (2020). DOI: 10.1021/acs.langmuir.0c00804

A-M. Pappa et al. “Optical and Electronic Ion Channel Monitoring from Native Human Membranes.” ACS Nano (2020). DOI: 10.1021/acsnano.0c01330

Researchers have developed a human cell ‘membrane on a chip’ that allows continuous monitoring of how drugs and infectious agents interact with our cells, and may soon be used to test potential drug candidates for COVID-19.

This type of screening is typically done by the pharmaceutical industry with live cells, but our device provides an easier alternative

Róisín Owens

Susan Daniel/Cornell ̽��ֱ��

Schematic of membrane on a chip device

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Women in STEM: Dr Anna-Maria Pappa

sc604 — Thu, 05 Sep 2019 06:00:00 +0000

I strongly believe that through diversity comes creativity, comes progress. I qualified as an engineer in the Department of Chemical Engineering at Aristotle ̽��ֱ�� of Thessaloniki, Greece, and went on to earn a Master’s Degree in Nanoscience and Nanotechnology from the same university. My PhD is in Bioelectronics from École des Mines de Saint-Étienne in France, and a key moment for me was when I left home to study abroad. Leaving my comfort zone for something unknown was very difficult in the beginning, but proved to be an invaluable experience. I met people from all over the world with different cultures and mind-sets, stretched my mind and expanded my horizons.

I find it very difficult to be around like-minded people; I always look for those with different views. I’m working on a drug discovery platform using bioelectronics, and my work sets out to improve and accelerate drug discovery by providing novel technological solutions for drug screening and disease management. My research focuses on the application of a new class of electronic materials and devices that could replace the in-vitro drug screening assays currently used in medical diagnoses with electronic arrays similar to the electronic chips found in mobile phones. These could quickly assess the health of our cells, outside of our bodies.

As an engineer, creating solutions to important yet unresolved issues for healthcare is what truly motivates me. I hope my research will lead to a product that will impact healthcare. ̽��ֱ��convergence of new technologies with life sciences will revolutionise both diagnosis and therapy. I imagine a healthcare system where the standard one-size-fits-all approach shifts to a more personalised and tailored model.

My most interesting project is one that is working to tackle the global challenge of antimicrobial resistance from a technological standpoint. We are developing biomimetic bacterial membranes on top of our devices and screening newly synthesised antibiotics. Investigating drug-bacterial membrane interactions allows us to directly test the efficacy of known drugs on bacterial resistant strains, as well as allowing us to better understand the action of novel drugs on the membrane properties, and ultimately aid the design and synthesis of target-specific antibiotics.

I joined Cambridge as a postdoctoral researcher in 2017. My daily routine involves some lab work in the Department of Chemical Engineering and Biotechnology, a lot of reading and writing, and some project management. I spend time in the Maxwell Centre too, where I participate in an entrepreneurship program called Impulse, exploring all the aspects of technology transfer.

Being part of a ̽��ֱ�� where some of the world's most brilliant scientists studied and worked is invaluable. Cambridge combines a historic and traditional atmosphere with cutting edge technological and scientific research in an open, multicultural society. ̽��ֱ��state-of-the-art facilities, and the openness in innovation and collaborations, along with great science, provide a unique combination that can only lead to excellence. I also travel frequently for conferences, as well as visiting other laboratories across Europe, the United States and Saudi Arabia. When you work in a multidisciplinary field it is essential to establish and keep good collaborations; since this is the only way to achieve the desirable outcome.

To be successful in a postdoctoral role requires management, teaching, networking, proposal writing and travelling. ̽��ֱ��amount of time you get to spend in the lab drops significantly compared to the PhD research period. This is in part due to the fact that you are more experienced, thus more efficient, and since you are more independent in research you need to be on top of things.

I think it’s absolutely vital, in every opportunity, for all of us to honour and promote girls and women in science. In October 2017 I was delighted to be awarded a L'Oréal-UNESCO For Women in Science Fellowship, an award that honours the contributions of women in science. For me, the award not only represents a scientific distinction but also gives me the unique opportunity, as an ambassador of science, to inspire and motivate young girls to follow the career they desire. Unfortunately, women still struggle when it comes to joining male-dominated fields, and even to establish themselves later at senior roles. We still face stereotypes and social restrictions, even if it is not as obvious today as it was in the past. This is in part due to the fact that still, the key senior roles are predominantly male-occupied, and so there is a lack of female role models as well as female mentality. This makes it harder for women to believe in themselves and achieve their goals.

A question I always ask during my outreach activities at schools is ‘do look like a scientist?’ ̽��ֱ��answer I get most times is ‘no’! I think this misperception of how professionals in STEMM look, or about what they actually do on a daily basis is what discourages girls early on to follow STEMM careers. This needs to change. On top of that, my advice to women would be to be open, never underestimate themselves and never be put off by stereotypes especially in male-dominated industries. There are excellent examples of highly successful women – leaders in their fields - who managed to excel despite the difficulties. Importantly, many of them successfully combined career and family.

Dr Anna-Maria Pappa is a postdoctoral researcher in the Department of Chemical Engineering and Biotechnology and holds the Oppenheimer Research Fellowship and Maudslay-Butler Research Fellowship from Pembroke College. Her research is focused on the global challenge of antimicrobial resistance.

Anna-Maria Pappa

Yes

Low-cost plastic sensors could monitor a range of health conditions

sc604 — Fri, 22 Jun 2018 18:00:00 +0000

̽��ֱ��sensor can measure the amount of critical metabolites, such as lactate or glucose, that are present in sweat, tears, saliva or blood, and, when incorporated into a diagnostic device, could allow health conditions to be monitored quickly, cheaply and accurately. ̽��ֱ��new device has a far simpler design than existing sensors, and opens up a wide range of new possibilities for health monitoring down to the cellular level. ̽��ֱ��results are reported in the journal Science Advances.

̽��ֱ��device was developed by a team led by the ̽��ֱ�� of Cambridge and King Abdullah ̽��ֱ�� of Science and Technology (KAUST) in Saudi Arabia. Semiconducting plastics such as those used in the current work are being developed for use in solar cells and flexible electronics, but have not yet seen widespread use in biological applications.

“In our work, we’ve overcome many of the limitations of conventional electrochemical biosensors that incorporate enzymes as the sensing material,” said lead author Dr Anna-Maria Pappa, a postdoctoral researcher in Cambridge’s Department of Chemical Engineering and Biotechnology. “In conventional biosensors, the communication between the sensor’s electrode and the sensing material is not very efficient, so it’s been necessary to add molecular wires to facilitate and ‘boost’ the signal.”

To build their sensor, Pappa and her colleagues used a newly-synthesised polymer developed at Imperial College that acts as a molecular wire, directly accepting the electrons produced during electrochemical reactions. When the material comes into contact with a liquid such as sweat, tears or blood, it absorbs ions and swells, becoming merged with the liquid. This leads to significantly higher sensitivity compared to traditional sensors made of metal electrodes.

Additionally, when the sensors are incorporated into more complex circuits, such as transistors, the signal can be amplified and respond to tiny fluctuations in metabolite concentration, despite the tiny size of the devices.

Initial tests of the sensors were used to measure levels of lactate, which is useful in fitness applications or to monitor patients following surgery. However, according to the researchers, the sensor can be easily modified to detect other metabolites, such as glucose or cholesterol by incorporating the appropriate enzyme, and the concentration range that the sensor can detect can be adjusted by changing the device’s geometry.

“This is the first time that it’s been possible to use an electron accepting polymer that can be tailored to improve communication with the enzymes, which allows for the direct detection of a metabolite: this hasn’t been straightforward until now,” said Pappa. “It opens up new directions in biosensing, where materials can be designed to interact with a specific metabolite, resulting in far more sensitive and selective sensors.”

Since the sensor does not consist of metals such as gold or platinum, it can be manufactured at a lower cost and can be easily incorporated in flexible and stretchable substrates, enabling their implementation in wearable or implantable sensing applications.

“An implantable device could allow us to monitor the metabolic activity of the brain in real time under stress conditions, such as during or immediately before a seizure and could be used to predict seizures or to assess treatment,” said Pappa.

̽��ֱ��researchers now plan to develop the sensor to monitor metabolic activity of human cells in real time outside the body. ̽��ֱ��Bioelectronic Systems and Technologies group where Pappa is based is focused on developing models that can closely mimic our organs, along with technologies that can accurately assess them in real-time. ̽��ֱ��developed sensor technology can be used with these models to test the potency or toxicity of drugs.

̽��ֱ��research was funded by the Marie Curie Foundation, the KAUST Office of Sponsored Research, and the Engineering and Physical Sciences Research Council.

Reference:
A.M. Pappa et al. ‘Direct metabolite detection with an n-type accumulation mode organic electrochemical transistor.’ Science Advances (2018). DOI: 10.1126/sciadv.aat0911

An international team of researchers have developed a low-cost sensor made from semiconducting plastic that can be used to diagnose or monitor a wide range of health conditions, such as surgical complications or neurodegenerative diseases.

This work opens up new directions in biosensing, where materials can be designed to interact with a specific metabolite, resulting in far more sensitive and selective sensors.

Anna-Maria Pappa

KAUST

Polymer biosensor

Researcher profile: Anna Maria Pappa

I strongly believe that through diversity comes creativity, comes progress. I qualified as an engineer, and later earned my Master’s degree at Aristotle ̽��ֱ�� of Thessaloniki in Greece. My PhD is in Bioelectronics from École des Mines de Saint-Étienne in France and leaving my comfort zone to study abroad proved to be an invaluable experience. I met people from different cultures and mindsets from all over the world, stretched my mind and expanded my horizons.

Now, I always look for those with different views. I travel frequently for conferences and visit other laboratories across Europe, the United States and Saudi Arabia. When you work in a multidisciplinary field it is essential to establish and keep good collaborations: this is the only way to achieve the desired outcome.

Being part of a ̽��ֱ�� where some of the world's most brilliant scientists studied and worked is a great privilege. Cambridge combines a historic and traditional atmosphere with cutting-edge research in an open, multicultural society. ̽��ֱ��state-of-the-art facilities, the openness in innovation and strong collaborations provide a unique combination that can only lead to excellence.

As an engineer, creating solutions to important yet unresolved issues for healthcare is what truly motivates me. I’m working on a drug discovery platform using bioelectronics, and my work sets out to improve and accelerate drug discovery by providing novel technological solutions for drug screening and disease management. I hope my research will lead to a product that will impact healthcare. In the future, I imagine a healthcare system where the standard one-size-fits-all approach shifts to a more personalised and tailored model.

I’m a strong advocate for Women in STEMM, and in October 2017 I was awarded a L'Oréal-UNESCO For Women in Science Fellowship, an award that honours the contributions of women in science. For me, the award not only represents a scientific distinction but also gives me the unique opportunity, as an ambassador of science, to inspire and motivate young girls to follow the career they desire.

I think it’s absolutely vital, at every opportunity, for all of us to honour and promote girls and women in science. Unfortunately, women still struggle when it comes to joining male-dominated fields, and even to establish themselves later at senior roles. We still face stereotypes and social restrictions, even if it is not as obvious today as it was in the past. A question I always ask girls during my outreach activities at schools, is, ‘do I look like a scientist?’, and the answer I most often get is no! I think this misperception of what STEMM professionals look like, or of what they actually do on a daily basis is what discourages girls early on to follow STEMM careers. This needs to change.

Yes

‘Women scientists have built our world. It’s time to invest in them’ – ̽��ֱ��Cambridge women campaigning for gender equality in science

Anonymous — Sun, 11 Feb 2018 08:00:00 +0000

It’s unlikely, as she wrote these words, that Dr Marie Sklodowska-Curie ever imagined the ongoing pathways of progress she had catalysed. Today, the United Nations’ International Day of Women and Girls in Science, the pioneer who paved the way for generations of women to pursue careers in science, technology, engineering, mathematics and medicine (STEMM) is one of the many successful women whose work is being celebrated around the world.

̽��ֱ��first person in history to receive two Nobel Prizes (her first was in physics; followed by the award for chemistry) remains an inspiration to scientists of all disciplines. Among them is Dr Karen Stroobants, a postdoctoral researcher in the Centre for Protein Misfolding Diseases, based in Cambridge’s Department of Chemistry. Her research focuses on the proteins associated with Alzheimer’s, Parkinson’s and other neurodegenerative diseases.

She said: “ ̽��ֱ��day I learned about Marie Curie, I came home and told my mother I was going to become a chemist … I have been intrigued by her life path and accomplishments from the first time I heard about her, and she remains my most important role model.”

Yet more than a century after Sklodowska-Curie became the first woman to win a Nobel Prize, her words hold particular significance when viewed through a different lens. ̽��ֱ��UN’s global event was established in response to the gender divide in the scientific community, in a bid to help address the continuing disparity that exists across the board.

In the United Kingdom women currently account for 24% of those working in the core STEM industries such as construction, information and communication technology and manufacturing. Women make up just 11% of the total number of professional engineers, and 42% of science professionals such as geologists, physicists and biochemists.

In his message about the event, the UN’s Secretary General António Guterres, himself a trained engineer and former maths teacher, said: “Both girls and boys have the potential to pursue their ambitions in science and mathematics, in school and at work. But systemic discrimination means women occupy less than 30 per cent of research and development jobs worldwide. We need concerted, concrete efforts to overcome stereotypes and biases. One starting point is banishing the predominantly male images of scientists and innovators on social media, in textbooks and in advertising.”

“We need to encourage and support girls and women to achieve their full potential as scientific researchers and innovators. Women and girls need this, and the world needs this, if we are to achieve our ambitions for sustainable development on a healthy planet. Throughout history, from Hildegard of Bingen to Wangari Maathai, women scientists have built our world. It’s time to support and invest in them.”

Stroobants agrees that more needs to be done before gender equality is achieved.

She said: “There is a need for initiatives not only to stimulate young girls to take up STEMM directions, but as importantly, also to stimulate young female professionals to take up leadership roles. Putting these issues in the spotlight is very important as it increases awareness, which is the first requisite for positive action.”

“Although programmes have been set up within institutions and universities to address the gender imbalance in academia specifically, I believe more general societal changes will have a larger impact.”

“Changes that contribute to a more gender balanced society will result in an increased number of female scientists. ̽��ֱ��girl-boy mentality gets fed to our children from a very early age, with gender-specific toys, activities and behaviour. I believe there are huge opportunities for behavioural scientists to address many of these issues.”

Stroobants also believes that teachers play a key role in helping to motivate and inspire younger students to study STEMM subjects.

“Good teachers, that share their interest in the world around them and are accessible for all children, are of vital importance to motivate youngsters to take up studies in the sciences. Female teachers, as role models, can further stimulate girls in particular to see the feasibility of pursuing a STEMM career.”

̽��ֱ��drive to motivate girls to study science is shared by many at the ̽��ֱ��. Dr Anna-Maria Pappa, from the Department of Chemical Engineering and Biotechnology, was recently awarded a L'Oréal-UNESCO for Women in Science Fellowship, and has spoken of her commitment to encouraging young girls to study STEMM subjects.

She said: “I think it’s absolutely vital, at every opportunity, for all of us to honour and promote girls and women in science. Each one of us should in every way that we can inspire girls to pursue an education in science, as well as support women’s right to equal opportunities in every sector of professional life.”

Cambridge has been home to a wealth of noteworthy female scientists. Among them is the chemist Rosalind Franklin, who played a vital early role in the discovery of the structure of DNA. ̽��ֱ��notebook she used to record her original findings is now held at the Churchill Archives Centre. Other female scientists whose papers are now held at the archives include Dame Enid Russell Smith, who played an instrumental role in setting up the National Health Service, the physicist Lise Meitner, and Mavis Beaty, a codebreaker who worked at Bletchley Park during the Second World War. ̽��ֱ��documents include notebooks, working papers, lecture notes and personal correspondence.

Natalie Adams in a Senior Archivist at the College. She said: “ ̽��ֱ��wonderful thing about archives is that they give the sense of the person as a whole, they don’t just focus on one element.”

“ ̽��ֱ��growing collection of documents created by women in science is a great asset to the archives. It’s interesting that often the papers by female scientists are more popular than those written by their male counterparts.”

“I think it’s often the case that people recognise that many of these women didn’t receive the recognition they deserved during their lifetime, and people today are interested in the reasons behind this and learning more about the culture in which these women worked.”

Beyond the ̽��ֱ��, other projects and initiatives are in place to help women build successful careers in science. ̽��ֱ��Cambridge Association for Women in Science and Engineering (CamAWiSE) is a regional network that provides opportunities for women in STEMM to meet and provide peer support and guidance. They also help women who want to return to work following a career break.

“We have a deficit of engineers and scientists in the UK, and at the same time we are losing women scientists every year,” said Aldara Dios, the orgnaisation’s coordinator. “Not only do fewer women follow STEMM careers than men but they also abandon their professions more. We are not only losing numbers, but also diversity.”

“Glass ceilings, unconscious bias, gender wage gap, work-life balance, lack of role models, and not inclusive workplaces are some of the challenges women in STEMM face.”

“ ̽��ֱ��UN's International Day of Women and Girls in Science is a powerful initiative. It helps visualise these problems and forces conversation on the topic at least one day a year.”

Cathy Sorbara is the current co-chair of the association. She holds a PhD in Medical Life Science and Technology, and is the Chief Operating Officer of Cheeky Scientist, a global organisation that works to help PhD graduates transition into industry.

̽��ֱ��work that CamAWiSE does to provide a network of support is something that Cathy feels is an important element in helping women to succeed. She said: “I think there is a desperate need for mentorship and support for women to stop them falling through the leaky pipeline, both in academia and in industry.”

Sorbara is committed to making changes to the scientific community, and on Tuesday will embark on the 2018 Homeward Bound expedition to Antarctica. This is the culmination of a year-long course to provide female scientists with the skills they need to be leaders in their field. ̽��ֱ��initiative aims to build a network of women over the next ten years who will go on to occupy leadership roles in STEMM disciplines.

Referring to the UN event, Sorbara says anything that raises awareness of female scientists is a positive thing.

She said: ‘I think we’ve come quite far, but we have quite a way to go. When I talk about this topic I’m always reminded of the quote ‘If you want to go fast go alone; if you want to go far go together’. This event is a positive thing because it will bring attention to the topic, but it’s also up to schools and companies to do all they can to leverage this and do more to help address the gender divide.”

Her words have echoes of Dr Sklodowska-Curie’s observation on the way of progress. ̽��ֱ��road to gender equality in the scientific community is proving to be neither swift nor easy, and today’s global event is not only an acknowledgement of the accomplishments and successes of so many female scientists, but also a reminder of the changes needed for progress towards gender equality be continue.

“I was taught that the way of progress is neither swift nor easy”.

I think it’s absolutely vital, at every opportunity, for all of us to honour and promote girls and women in science.

Anna-Maria Pappa

Women in Chemistry

Karen Stroobants

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes