14 October 2021

Meet the keynote speakers at ISBUC's 2021 Annual Meeting

lynn kamerlin robert tampe ed tate sebastian westenhoff ISBUC annual meeting 2021
From left: Professor Robert Tampé from Goethe University, Professor Lynn Kamerlin from Upsala University, Professor Ed Tate from Imperial College London and Sebatsian Westenhoff from the University of Gothenburg.

The 2021 ISBUC Annual Meeting will take place on October 29th and feature talks from four internationally renowned researchers. Here, you will find out who they are and what they will talk about.

Robert Tampé: Cellular Machineries and Supercomplexes in Immune Defense and Infectious Diseases

Robert Tampé studies the cellular machineries that are responsible for quality control within the cell. ‘These are complex machineries which are built and disassembled on a very fast time scale, so they are not static structures but they are involved in shaping cellular pathways on multiscales’.

By training, Tampé is a biochemist and has pioneered an approach that applies biochemistry at the single-cell level and then uses that as a platform to study biological structures and subcellular architectures. Tampé promotes a truly integrated approach to biology that brings together single-particle cryo-EM, x-ray diffraction, single-molecule spectroscopy, and super-resolution microscopy. ‘This is absolutely important because there is a richness at the border between disciplines. If you have two classical disciplines, I always say, go in between and you immediately gain much more’ says Tampé.  

 Not only is Tampé an ardent advocate for integrating multiple structural biology methods but he also advocates an approach that combines in vitro and in situ. ‘I like in vitro because it is the pure approach where you have all the single components, but in parallel we always try to see the cellular assemblies in situ, using elegant pullout assays to see how these complexes are really formed and shaped inside the cell’.

 Tampé overcomes the challenges of adopting such an integrated approach by always putting the research question first. One of the big big research questions that drives him is understanding the machineries that detect cancerous and virally-infected cells in the immune system. In Copenhagen, Tampé will speak on the machineries that regulate antigen processing; from the birth of an antigen, how it is translocated and trafficked, processed and stabilized before finally being released and recognized by T-Cells.

Lynn Kamerlin: Harnessing Conformational Dynamics and Computational Design to Generate Novel Enzymes

Lynn Kamerlin is a rising computational structural biologist, part of a new generation that is challenging the status quo of how we approach the study of biological structures and what we study. Her research centers around the evolution of enzymes. In particular, she is interested in the evolution of enzyme turnover rates where she has made breakthrough discoveries about the role of conformational (and, in particular, loop) dynamics. 

‘A lot of biologists think of loops as just lids, but we started noticing in several systems that the dynamics of the loops is what’s regulating turnover. They are not just lids, they are not just this thing that closes over the active site’ explains Kamerlin. Kamerlin’s research goal is to expose both how these dynamics work and how they regulate turnover. Taking things one step further, her research has also suggested at how we can modulate dynamics to change enzyme behaviour. The big question she is currently interested in is: ‘without touching the active site, without touching the catalytic residues, can we change the behaviour of the enzyme? Can we make an enzyme faster, or even slow it down?’

Kamerlin’s talk in Copenhagen will revolve around two case studies. First, she will show how loop dynamics regulate turnover rates and the role that conformational dynamics play in the evolution of enzymes. In the second part of her talk, she will show how you can use conformational dynamics in artificial evolution to create completely new enzymes. In this lengthy process, Kamerlin and her collaborators used ancestral reconstruction to predict the sequence of a Precambrian enzyme, reconstructed it in the lab, used the dynamics of the scaffold to identify completely new and non-natural catalytic sites and then optimized the resulting enzymes using computational approaches to obtain turnover numbers approaching those of naturally occurring enzymes.

Ed Tate: Protein modification: from chemical biology to drug discovery

Ed Tate is a chemical biologist at Imperial College London whose work investigates the emergent functions of proteins. That is to say, those functions that are not directly encoded in the genome but emerge through processes of post-translational modification and enzyme activity. For Ed, this is a significant frontier for biology. We need new tools that allow us to see how a protein is modified post-translationally, how an enzyme behaves in a particular tissue or how two proteins will interact.

To develop these tools, Ed has combined his background in chemistry with biological approaches in order to develop different ways of looking at proteins. One of the key tools he uses is proteomics, a mass spectrometry technique that allows one to identify and quantify which proteins are in a sample. But where traditional proteomics methods don’t tell you what state your protein is in, Ed has added a layer of information about the post-translational modification states of the proteins. ‘We are combining approaches taken from chemical biology with proteomics to enhance the information that we are getting from proteomics data. We add the ability to interrogate each of these PTM states in the proteomics data’ says Tate.

Ed’s recent work has primarily focused on post-translational lipid-modifications of proteins, which anchor them to membranes. These are difficult targets for structural biology but Ed’s tools allow him to capture how these modifications are added by enzymes to proteins across the proteome. ‘Fundamentally we have learnt what these enzymes do, what the modifications are added to and what function they have and on top of that we have managed to translate some of that work to identify new drug targets’.

In Copenhagen, Ed will walk about this work on protein lipidation, outlining a project from early discovery through to a spin out company that is now heading into clinical trials. He will also speak on some of his recent work involving cryo-EM, where his group has worked with collaborators in Oxford to solve a complex 10-multipass transmembrane protein.

Sebastian Westenhoff: Time-resolved crystallography of phytochrome proteins: the 'eyes of plants' resolved at atom scale resolution.  

Sebastian Westenhoff is a young star whose work is already having a big impact on the future of structural biology. Where traditional structural biology has largely studied proteins in their resting states, Westenhoff and his group have been developing tools to record the entire time series of what happens when a protein performs its specific task.

‘It is important for understanding how the protein actually functions. One can compare this to a car. Taking the blueprint of the car, you could draw some conclusions about how a car functions, but to really understand how it works you have to see the car in motion; one has to observe the gears and parts engaging with another.’ To make films of protein in motion, Westenhoff uses a combination of time-resolved X-ray scattering, crystallography and spectroscopy, as well as the intense, femtosecond, hard X-ray pulses made available through X-ray Free Electron Lasers (XFELs) 

The proteins which Westenhoff is interested in are phytochrome proteins that exist in plants and bacteria and function to detect red light. For example, these proteins can detect when a plant is in the shadow or when a seed is close to the soil surface, both of which will trigger the plant to grow.

Not only are these proteins the eyes of the plant world making them an important subject for plant biology, but they have also proven themselves to be important biophysical model systems for studying conformational dynamics. ‘They are really good systems for filming proteins in action because you can trigger the reaction simply by light which has a huge advantage experimentally’ explains Westenhoff. Light-trigger proteins are thus spearheading the development of time-resolved structural techniques and - in the future - it is anticipated thatany number of protein compounds will become accessible by these methods. In his talk, Westenhoff will demonstrate how time-series of protein structures in action can reveal more detailed information about the inner working of proteins. 

By Lucy Holt.