Bioscience Research Group Seminar Series

Delivered by Dr Ruth Mackay (Mechanical and Aerospace Engineering, Brunel University London).

Date: 15 December 2021

In the past 18 months point of care (POC) diagnostics have become an everyday item used by millions in the UK and around the world. Nucleic Acid Amplification Testing (NAAT) is becoming increasingly popular within POC diagnostics due to the rapid, sensitive and specific results obtained. An integrated micro-engineered platform is under development for automated DNA extraction, isothermal amplification using micro volume samples. This has been used with respect to samples for Sexually Transmitted Infections (STI), poultry pathogens and most recently SARS-CoV-2. Sample preparation from varying matrices has been a bottleneck in the diagnostic procedure that has been overcome using alternative methods to the standard commercial extraction methods.

An extension of the STI work has been the development of a Vagina-on-a-Chip; a tool developed to give greater under understanding into bacterial vaginosis and it’s role in STI transmission. BV is characterised by an overgrowth of anaerobic bacteria, originally attributed to Gardnerella Vaginalis (GV), disrupting the typically dominant lactobacilli vaginal ecosystem, resulting in discomfort and vaginal discharge with fishy odour. Women with BV have higher risk of transmission of STI and poor perinatal outcome. In vitro models have been developed, including two-dimensional, organoid and animal models; however, researchers are calling for a more representative model to investigate BV. Over the past decade a new technology to replicate three-dimensional tissues has been established by microfluidic researchers, organ-on-a-chip (OOC). These in vitro models use microfluidic chips embedded with a scaffold and cells from specific organs. Using organ-specific forces and fluidic shear flow these micro-tissues can represent the physiological environment of the organ under investigation. Numerous OOC models have been developed (lung, gut, heart and brain). BV is a common condition that requires greater understanding and new treatments. OOC gives researchers in the field a way forward to create a model that represents the vagina in a way not seen before.

Please contact Maria Dimitriadi for further details.

Delivered by Dr Andrew Powell (School of Pharmacy Biomolecular Sciences, Liverpool John Moores University)

Date: 24 November 2021

Cells have exterior surfaces displaying numerous receptor molecules of the plasma membrane. These receptors are docking sites for proteins that mediate communication between cells (which if malfunctioning can cause disease) and microbes (which infect cells and can cause disease). A type of receptor molecule are carbohydrates (glycans) and a family of complex glycans are the glycosaminoglycans (GAGs). GAGs display immense structural heterogeneity that underpins their interaction with approaching 1000 proteins (including growth factors, cytokines, chemokines, enzymes and matrix proteins) and a collective of different microbes (including pathogenic SARSCov2 of Covid-19, the MRSA ‘superbug’ and Plasmodium falciparum of malaria). The challenge is to decipher information regarding structural specificity for protein and microbial interactions with GAGs. This information can then be used to develop novel, optimised glycotherapeutics/antimicrobials against different diseases associated with GAG-binding proteins or pathogenic microbes.

I will cover work on two particular cellular contexts: 1. Neurones and chemokines (patterning), and 2. skin epidermal keratinocytes and MRSA/cytokines (barrier infection, innate immunity and homeostasis), before discussing future directions within the latter context.

Please contact Maria Dimitriadi for further details.

Delivered by Dr Maija Hollmén (MedCity Research Laboratory, University of Turku, Findland)

Date: 27 October 2021

Significant discoveries in the field of tumorimmunology have revolutionised cancer treatment in the last few years and are now offering unforeseen prospects of cure for some patients. Despite these advances, the majority (up to 80%) of patients remain refractory to current immune checkpoint inhibitor therapy for mainly unknown reasons. Targeting macrophages to break the immune-tolerance of tumors and help activate host immune defenses is the next cutting edge in cancer immunotherapy. Macrophage-targeted therapies may be used as monotherapy or in combination with a variety of other treatments, and open entirely new therapeutic options for people without a cure. One such target is Clever-1 (also known as Stabilin-1 and FEEL-1), a large glycoprotein receptor that is expressed by immunosuppressive macrophages and monocytes, and which is involved in scavenging, angiogenesis and cell adhesion. Previously, we have found that the growth of multiple solid tumors in mice is significantly impaired when Clever-1 is genetically removed from macrophages. Moreover, immunotherapeutic Clever-1 blockade reactivated the anti-tumor CD8+T-cell response with comparable therapeutic efficacy to PD-1 checkpoint blockade.

Currently, a Clever-1 targeting humanized antibody, bexmarilimab, is in clinical development to evaluate its safety, tolerability and preliminary efficacy in patients with advanced solid tumors (Phase I/II; NCT03733990, MATINS).

Delivered by Dr Mustafa Ozel (Department of Clinical, Pharmaceutical and Biological Sciences
University of Hertfordshire)

Most companies in the food & pharma industries use conventional extraction methods such as those using solvents, or steam and hydro-distillation. Recent trends in extraction techniques have largely focused on minimizing the use of petroleum-based solvents. Recently, more efficient extraction methods, such as subcritical water extraction (SWE), supercritical fluid extraction (SFE), and microwave assisted extraction (MAE) have been used for the isolation of organic compounds from various plants. These extraction techniques are not only cheaper and faster, but being considered environmentally-friendly, they also enable these products to claim a green label. Having a green label is desirable to many customers.

Qualitative and quantitative analysis for natural products can be carried out using advanced analytical equipment such as the Electronic nose, GC-NCD/SCD (Nitrogen chemiluminescence detector and Sulphur chemiluminescence detector), 2 dimensional GC-MS and headspace GC-MS. Each system has its own advantages.

Delivered by Prof. Marta Filizola (Icahn School of Medicine at Mount Sinai, New York, USA)

Date: 23 June 2021

Prescription opioids such as oxycodone and morphine remain the gold standard for treating moderate to severe pain, notwithstanding the daunting number of unintentional opioid overdose fatalities mostly due to respiratory depression through the μ-opioid receptor (MOR), as well as their high potential for abuse liability. Since efforts to discover safer analgesics targeting MOR at the orthosteric site have encountered challenges, there is a need to discover potentially safer non-opioid alternatives while making opioid drugs safer to use. Molecular dynamics simulations leveraged by artificial intelligence-based methods have contributed an atomic-level understanding of how opioid drugs bind and activate this receptor, shedding light on the complexities of receptor pharmacology and thus informing the design of potentially improved opioid therapeutics. In this presentation, I will summarize recent efforts from my lab towards this goal.

Delivered by Dr Jonathan A. G. Cox (School of Biosciences, College of Health and Life Sciences, Aston University)

Date: 12 May 2021

Infections caused by Mycobacterium abscessus are increasing in prevalence in cystic fibrosis patients. This opportunistic pathogen′s intrinsic resistance to most antibiotics has perpetuated an urgent demand for new, more effective therapeutic interventions. In this talk, Dr Cox will explain what M. abscessus is and why it poses such a significant clinical challenge. He will then discuss his group’s progress in developing a new three-drug treatment for M. abscessus infection; increasing the susceptibility of the organism to amoxicillin, by repurposing the β-lactamase inhibitor, relebactam, in combination with the front line M. abscessus drug imipenem. He will explain how this synergy has been explored on a microbial and biochemical level, and talk about how these drugs are being clinically trialled in the UK as a last therapeutic option for patients where conventional treatment has proven unsuccessful.

Delivered by Dr Shoib Siddiqui (Clinical, Pharmaceutical & Biological Sciences University of Hertfordshire)

Date: 28 April 2021

Glycans (sugars/carbohydrates) are present on the surface of every cell. Sialoglycans (Sia) is the terminal sugar for the glycan chain present on the glycoproteins and glycolipids. Sia binds with a family of protein called Siglecs (Sialic Acid binding Immunoglobulin superfamily Lectins) and can modulate the immune responses. Siglecs can be immunoinhibitory or immune-activating in nature. We have recently shown that an engagement of Sia with inhibitory or activating Siglecs affect tumour growth (Stanczak, Siddiqui et al., JCI, 2018).

It has also been recently shown that the secretory protein HMGB1 is a Sia binding lectin and plays an important role in the pathogenesis of sepsis (Siddiqui et al., PNAS, 2021). Thus, using state of the art techniques, the Siglec-Sia axis and HMGB1-Sia axis have been shown to be emerging players in cancer and sepsis. In this seminar, I will talk about some of the ground-breaking discoveries in the field of sepsis and cancer and how to target Sialoglycans for the next generation therapeutic interventions.

Delivered by Dr Emmanouil Karteris (Division of Biomedical Sciences, Brunel University London)

Date: 24 March 2021

Delivered by Dr Eric Hill (School of Life & Health Sciences, Aston Research Centre for Healthy Ageing, Aston University)

Date: 24 February 2021

Alzheimer's disease (AD) is the most common form of dementia affecting around 36 million people worldwide. It is impossible to study such changes in the cells of living patients, and it is difficult to adequately study the disease in animals as they do not naturally develop the condition. A revolutionary technique now allows stem cells to be generated from the skin cells of individual patients. In this seminar Dr Hill will discuss the use of these induced pluripotent stem cells to generate functional brain models to study AD and how advancements in tissue engineering are allowing scientists to build complex neural circuits to study development and disease.

Delivered by Professor Peter Mullany (Microbial Diseases, UCL Eastman Dental Institute, Faculty of Medical Sciences)

Date: 20 January 2021

Mobile genetic elements (MGEs) can spread genes between bacteria, sometimes even between very distantly related organisms. In this talk I will illustrate, using examples taken from my research, the different types of MGEs and the effect they can have on bacteria and consequently on humans.

As well as providing challenges for humans MGEs offer many opportunities in the field of biotechnology. Evolution has equipped them with the ability to cross bacterial cell walls and membranes, to enter and genetically manipulate bacterial genomes. These abilities have been utilised by molecular biologists for the last 60 years or so to make huge advances in biological sciences. Furthermore, the response of the host bacteria to protect themselves from MGEs such as production of restriction enzymes and CRISPR Cas systems has also been used by scientists to revolutionise molecular biology.

I will give a brief example of some of our current work using CRISPR Cas systems to target antibiotic resistance genes on MGEs.

Delivered by Dr Caroline Formstone (Department of Clinical, Pharmaceutical & Biological Science, University of Hertfordshire)

Date: 09 December 2020

The skin provides a protective layer for the body against desiccation and external assault. How skin is built in the embryo has been long studied but little is known about how it encompasses the body. My research has shown that the skin emerges in mouse embryos just over half-way through gestation. The skin appears as a thickened tissue at the mid-flank of the embryo trunk which subsequently thins and spreads from the mid-flank towards the front of the embryo (ventral-side) and the back of the embryo (dorsal-side) eventually enclosing the embryo trunk 2-3 days later. I will provide evidence that skin enclosure of the embryo body requires both intrinsic and extrinsic processes. Overall, my research raises the hypothesis that failure to enclose the embryo body with skin may underlie some common birth defects of dorsal and ventral closure and importantly that extrinsic factors may reduce their prevalence.

Delivered by Prof. Ana-Nicoleta Bondar (Department of Physics, Freie Universität Berlin, Germany)

Date: 11 November 2020

The new SARS-CoV-2 virus is known to bind via the spike protein (protein S) to the human host ACE2 receptor followed by proteolytic activation of S. Structural signatures of conformations sampled by protein S were identified with graph-based algorithms in static structures and simulations of protein S. We found that the closed conformation of protein S has, at key functional sites, three-fold symmetrical H-bond clusters. Loss of three-fold symmetry as observed in open and closed conformations of the spike protein could facilitate conformational selection for receptor and protease interactions. Instead of discrete interaction pairs, the receptor-binding interface consists of an extensive interaction network that includes multiple groups from both protein S and ACE2, which could explain strong binding affinity and provide robustness.

Delivered by Dr. Bill Broadhurst (Department of Biochemistry, University of Cambridge)

Date: 14 October 2020

I will provide a brief introduction to protein dynamics on different timescales and ways of quantifying these processes, with a particular focus on NMR spectroscopy. I will then discuss an application to the conformational plasticity of ligand-bound ternary complexes of the beta1-adrenergic receptor, a model G-protein coupled receptor (Nature Communications (2020) 11, 669). After that I will describe some of my work on the dynamics of acyl carrier protein domains in modular polyketide synthase multienzyme complexes (Biochemical J (2016) 473, 1097-1110; Scientific Reports (2019) 9, 2325; Chemical Comm (2017) 53, 11457-11460).