Tag: University of Bristol

BBI International Webinar Series – Professor Elisa Franco, UCLA

Posted on by agatha.hewitt

The Bristol BioDesign Institute‘s newly imagined webinar series for 2021 has been designed as a platform to invite the best international speakers that are aligned to our core areas of interest. These include; biomolecular design and assembly in the cell, development and delivery of bioactive molecules, minimal biology towards cell-like systems, advanced computing and digital biology. You can find our upcoming speakers for the year on the International Webinar Series section of our website.

The first speaker of 2021 is Professor Elisa Franco from UCLA, with BBI Directors, Thomas Gorochowski and Dek Woolfson, panelling. The seminar is followed by an audience Q&A session, and then a one-to-one interview where Dr. Gorochowski asks Professor Franco questions about how she got into synthetic biology and her predictions for its future. 

You can watch Professor Franco’s seminar, on ‘Programming dynamic behaviors in molecular systems and materials‘ below, or on the BBI YouTube Channel.

Abstract – Biological cells adapt, replicate, and self-repair in ways that are unmatched by man-made devices. These processes are enabled by the interplay of receptors, gene networks, and self-assembling cytoskeletal scaffolds. Taking inspiration from this architecture, we follow a reductionist approach to build synthetic materials by interconnecting nucleic acid components with the capacity to sense, compute, and self-assemble. Nucleic acids are versatile molecules whose interactions and kinetic behaviors can be rationally designed from their sequence content; further, they are relevant in a number of native and engineered cellular pathways, as well as in biomedical and nanotechnology applications. I will illustrate our approach with two examples. The first is the construction of self-assembling DNA scaffolds that can be programmed to respond to environmental inputs and to canonical molecular signal generators such as pulse generators and oscillators. The second is the encapsulation of these dynamic scaffolds in droplets serving as a mimic of cellular compartments. I will stress how mathematical modeling and quantitative characterization can help identify design principles, guide experiments, and explain observed phenomena.

Druggable pocket discovered in SARS-CoV-2 Spike protein could stop virus spread

Posted on by agatha.hewitt

An international team of scientists, led by University of Bristol Professors Christiane Schaffitzel and Imre Berger, have unearthed a druggable pocket in the SARS-CoV-2 Spike protein that could be used to stop the virus in its tracks. ‘Spike protein’ refers to the multiple copies of glycoprotein that surround SARS-CoV-2. These ‘spikes’ bind to human cells, allowing the virus to penetrate the cells and replicate, damaging as they go. The collaborative study of SARS-CoV-2 is comprised of experts from Bristol UNCOVER Group, Bristol biotech Imophoron Ltd, the Max Planck Institute in Heidelberg and Geneva Biotech Sàrl.

Professor Imre Berger, Max Planck Bristol Director and Bristol BioDesign Institute Director

The team analysed the SARS-CoV-2 Spike protein at near atomic resolution by applying electron cryo-microscopy (Cryo-EM) and Oracle’s high-performance cloud computing to produce a 3D image of the virus’s molecular composition. After getting a look at the virus up-close, the scientists spotted a potential ‘game changer’ in defeating the current pandemic.

The researchers spotted the presence of a free fatty acid; linoleic acid (LA), hidden away in a pocket within the Spike protein. LA is vital to most cellular functions in humans. It is not naturally produced by the body, so humans must intake LA through diet. The acid helps to maintain cell membranes in the lungs, and regulates inflammation and immune modulation, which are all the functions that are implicated in Covid-infected patients. Professor Berger, Director of the Max Planck Bristol Centre for Minimal Biology, confirms that “the virus that is causing all this chaos, according to our data, grabs and holds on to exactly this molecule – basically disarming much of the body’s defences.”

Professor Christiane Schaffitzel from the School of Biochemistry

Professor Schaffitzel, from the University of Bristol’s School of Biochemistry, explained: “From other diseases we know that tinkering with LA metabolic pathways can trigger systemic inflammation, acute respiratory distress syndrome and pneumonia. These pathologies are all observed in patients suffering from severe COVID-19. A recent study of COVID-19 patients showed markedly reduced LA levels in their sera.”

The exploitation of the druggable pocket containing LA in SARS-CoV-2 could be the key to manipulating the virus. The discovery of a druggable pocket has previously been successfully exploited in rhinovirus, which causes the common cold. In rhinovirus, small molecules were tightly bound to the pocket to distort its molecular structure, and prevent its infectivity in human cells. The team are optimistic that their discovery of a similar pocket in SARS-CoV-2 can be used to develop small molecule anti-viral drugs against it.

Professor Berger adds: “Our discovery provides the first direct link between LA, COVID-19 pathological manifestations and the virus itself. The question now is how to turn this new knowledge against the virus itself and defeat the pandemic.”