Demystifying maths and stats for Bioscientists 2018

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From 21st-25th of May 2018, our PhD students Jasmine Bird and Andrea Giachino attended the STARS-sponsored training course “Demystifying Mats and Stats for Bioscientists” at Newcastle University, hosted by Prof Jarka Glassey. It was an invaluable development experience, packed full with state-of-the-art statistical techniques, experimental design, and private-sector golden standards.
Congratulations to Andrea for receiving the Best Presentation award (picture): his group’s presentation “Assessment of Bacterial Growth Parameters” showcased the implementation of advanced statistical methods to improve their research data.

Best presentation award at “Demystifying Maths and Stats for Bioscientists” 2018. From left to right: Prof Jarka Glassey, Joan Cortada Garcia, Andrea Giachino, Gaik Sui Kee, and Martina Daute.

Andrea says:
I feel like I learnt so much from this course, and I will be looking at my data with different eyes from now on. It made a huge contribution to my skills as a researcher, improving my experimental design, data analysis, and critical thinking. What I liked the most was the amazing range of contributions from the private sector, which will benefit my long-term career goals. And of course, winning the final competition felt so rewarding!

Jasmine says:
I learnt a lot from this course, especially in terms of thinking about my data differently and more critically. This will benefit my data analysis in the future. The range of academic and industrial perspectives of modern problems in Biotechnology kept things interesting and gave me useful insight into how both areas tackle problems.

Structure and Biochemistry of a bacterial microcompartment enzyme

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Looking at enzyme encapsulation and why it matters in bacteria

Bacterial microcompartments are small protein structures that encapsulate various enzymes and substrates. This blog will look at our lab’s recent paper on an enzyme from a bacterial microcompartment, what we learned from it and where to take this research next.

Before discussing why bacterial cells need microcompartments, or even what they are, let’s look at why cells would need to compartmentalise themselves at all. All cell types across all kingdoms of life have some internal structure and capacity for sorting their contents. Cells package their DNA, enzymes for metabolism and chemicals into discreet compartments, with the purpose of making the cell more efficient and protecting it from toxic chemicals produced by the reactions happening inside. Bacterial cells do this via bacterial microcompartments (BMCs), which are protein shells that self-assemble and compartmentalise enzymes and their substrates in a wide range of different bacteria, from gut microbes to bacteria found in the soil and sea. Continue reading →

Moving day

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The Marles-Wright Lab will be moving to the School of Biology at Newcastle University this summer, where Jon will be taking up a position as Senior Lecturer in Microbial Biotechnology. It has been a brilliant few years working at Edinburgh getting the lab up and running and I shall miss all of my colleagues there, but I am looking forward to some new adventures in Newcastle.  We’re still hiring a Post-Doc to work on the BBSRC funded project with Dr Dave Clarke in the School of Chemistry, University of Edinburgh. We’re also looking for self-funded PhD students to join the lab on some exciting structural/synthetic biology projects.

Streptoccus mutans sortase A structure

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SrtA1-300x300Interest Statement: This work was funded in part by the Wm. Wrigley Jr. Company.

We recently determined the structure of the Streptococcus mutans sortase A protein in collaboration with the Campopiano group in the School of Chemistry at the University of Edinburgh. This work was part of the PhD project of one of Dom’s students who was working on natural product inhibition of bacterial pathogens and was sponsored by the Wm. Wrigley Jr. company. Our crystal structure was used to model the binding of trans-chalcone in the active site of the protein to help understand the mechanism of its inhibition of this protein. Sortases are found on the surface ofGram positive bacteria and attach certain proteins to the bacterial cell wall. These cell wall associated proteins are implicated in virulence and the formation of biofilms, and by inhibiting their attachment to the cell these proteins cannot function.

Trans-chalcone is a member of a huge family of flavonoid natural products that are found in liquorice and turmeric root to name just a few sources. In this paper we use biochemical assays and mass spectrometry to show that trans-chalcone irreversibly binds to Sortase A from the oral bacterial Streptococcus mutans. We modelled the interaction of this molecule with the crystal structure to show that larger chalcone molecules could be accommodated in the active site of this protein and that this could be used to select Sortase A specific inhibitors based on differences in the active-site cleft between the different classes of Sortase proteins.

This paper was reported by the Scottish Daily Mail:

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The X-ray crystallographic data was all collected at Diamond Light Source as part of the University of Edinburgh BAG and was reported on the Diamond Light Source front page. Here’s the official University of Edinburgh press release.

100 words

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Since my last post in July the Marles-Wright Lab has grown with the addition of two new PhD students, Didi and Laura, who joined Kirsten and me in September. After a conversation with guest seminar speaker this term where both Laura and I struggled to sum up her project succinctly, I challenged everybody in the group to come up with a 100 word summary of their project that they could use at a Christmas party, or in casual conversation with an FRS.

Here they are (unedited) for your consideration.

Laura

My project is based on bacterial microcompartments, which are proteinaceous structures that compartmentalize various metabolic processes such as fucose and rhamnose, or ethanolamine breakdown in a wide range of bacteria. The ultimate aim of my project is to synthesize an artificial fucose and rhamnose compartment in Clostridium phytofermentans, however to achieve this more information is needed about how the shell proteins and enzymes that make up these compartments are recruited and in what ratio are they combined. To try and answer some of these questions I will develop a shell protein localization sequence vector that will hopefully allow me to screen large numbers of signal sequences to find binding partners between microcompartment proteins.

Didi

Bacterial microcompartments (BMCs) are cytosolic, polyhedral organelles with a proteinaceous shell and enclosed enzymes, which protect the cell from volatile or toxic intermediates (propionaldehyde/acetaldehyde) or active oxygen. I focus on the microcompartments from Rhodospirillum rubrum. Through understanding how BMCs self-assembling we can modify them to contain potential therapeutic cargoes. To understand the protein assembly and metabolic pathway within the BMC, I will determine the substrate inducing the BMC production, followed by understanding protein components and interactions. Then I will propose a metabolic model of BMC based on transcriptional, protein and metabolic analysis. Finally, I will clone the BMC or construct functional empty microcompartments in vitro.

Kirsten

My research focuses on the most basic microcompartment, the empty shell. I am involved in engineering these minimal compartments consisting of shell proteins only to initially study their structure and the influence of tags on the formation and size of the compartments. Subsequently, we aim to design compartments filled with either molecular probes to further analyse their properties, or compartments containing different enzymes to study the effect of encapsulation on various enzymatic reactions. Apart from the engineering aspect of this project, I am involved in designing the relevant assays to study the compartments and their cargo using biochemical as well as microscopy based techniques.

Help, I’m a Scientist!

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This post is coming some weeks after the end of the latest I’m a Scientist event in March, and with the recent change in weather it seems like it was an entire season away. I was the first evictee from the Drug Discovery Zone; for a nice blog from one of the winners read this by Tom Branson. This is my story on how not to do IAS (tl;dr – fully commit and clear your schedule, or don’t do it).

I’ve been on the mailing list for IAS for about two years, but for various reasons I never got round to participating. I finally entered the Drug Discovery Zone this January, as my diary was looking pretty clear after having submitted a fellowship application and two big grants just before Christmas (all unsuccessful if you’re interested in keeping score). Continue reading →

College of Science and Engineering Sandpit

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Judging by my recent blog posts, the last couple of months seem to have been focused on professional development and networking activities to the exclusion of everything else. This isn’t entirely true as there’s an obvious selection bias at work in what I am writing about. These events have been interesting asides to the daily life of junior faculty (the staff meetings, teaching, people management, outreach, and the fleeting moments I actually get to spend in the lab doing science), which isn’t hugely interesting stuff to blog about. Continue reading →

Heriot-Watt Crucible V Session 3: Day 2

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The closing session of the H-W crucible and culmination of the days over the last three months I have spent with my fellow cruciblists and facilitators was held in the Millenium Dome-like Dynamic Earth centre next to the Scottish Parliament. It’s an attractive building in a beautiful location, next to my new favourite piece of modern architecture, but it has the strong imprint of being a Millennium project about it. Saying that, due in part to the excellent stewardship of the scientific director Dr Stuart Monro, it has been extremely successful and gives a wonderful sense of the role that geology plays in shaping life on Earth and in particular Scotland, the centre being nestled at the foot of the Salisbury crags with magnificent views of the landscape. Continue reading →