The SPP2191 has reserved funds to accelerate the development of an excellent senior postdoctoral fellow towards independence. The aim of this program is to support a postdoctoral fellow associated with an SPP2191 host laboratory to develop an independent research program that will enable them to potentially submit a competitive proposal for the next 3-year funding period of the SPP2191.
Here we proudly present you the two awardees: Herman Fung & Lars Hubatsch
Who are you?
My scientific life began in Australia, and has since taken me to the UK, the US, and now to Heidelberg, Germany. Over time, I have developed a strong interest in how genetic material is organised inside cells. A big part of my work now is about using structural biology and biophysics to understand the mechanisms behind this. In my PhD, I studied the molecular mechanisms of genome packaging in DNA viruses by X-ray crystallography, NMR, single-particle cryo-EM and single-molecule localisation microscopy. In my postdoc now at the European Molecular Biology Laboratory in Heidelberg, I am using cryo-electron tomography (cryo-ET) as a means to study molecular structures inside cells, with a focus on ribosomal DNA transcription and the architecture of the nucleolus. To help this work, I am also developing methods to streamline and automate the preparation of thin lamella specimens for cryo-correlative electron tomography, as a means to target specific structures inside the cell for imaging.
What project do you plan to work on while being supported by the award money?
In my future research, I would like to capture the structure of chromatin inside cells by cryo-ET, and elucidate how phase separation contributes to genome structure and function. A current major limitation of cryo-ET is that it is difficult to identify molecules in the observed cellular landscape, unless the molecule has a known shape and a certain size (e.g. ribosomes). This poses a particular challenge for the study of flexible, disordered molecules known to be key in driving liquid-liquid phase separation. With the support of this award, I would like to overcome this limitation by developing a new localisation method based on genetically encoded multimeric nanoparticles (GEMs) — self-assembling protein structures with a defined size and shape that would be easily detectable by cryo-ET. The main challenge ahead will be to identify a GEM protein that will robustly form particles and can be efficiently imported into the nucleus for the tagging of nuclear proteins. In the Mahamid lab, and in collaboration with the Cüylen lab, I plan to tackle this by screening a selection of proteins and testing their potential for protein tagging in the nucleolus of human cells.
How do you prepare for applying for the second funding round?
In my future independent work, I would like to understand how phase separation contributes to chromatin structure. Phase separation has been known to underlie both gene activation and repression, for example, in the formation of transcription hubs on super-enhancers, and in the establishment of heterochromatin domains at the nuclear lamina. The labelling strategy developed here will provide an unprecedented and powerful tool for cryo-ET analysis of these chromatin condensates, and will, therefore, form the backbone for my future application.
MPI for Molecular Cell Biology and Genetics Dresden
Who are you?
|2021-present||Hyman lab, MPI for Molecular Cell Biology and Genetics, Dresden|
|2018-2021||Postdoc Weber/Jülicher groups, MPI for the Physics of Complex Systems, Dresden|
|2013-2018||Graduate Student Goehring lab, Francis Crick Institute, London|
|2011-2012||Academic exchange, Université Paris Sud|
|2008-2013||Diplom Physics, Dresden University of Technology|
I am trained as a biological physicist and started out working on models for DNA repair in the lab of Stephan Grill (MPI-CBG, Dresden). Subsequently, I pursued a PhD in Nate Goehring’s group (Francis Crick Institute, London), investigating size adaptions of polarity networks, both theoretically and experimentally, in the C. elegans embryo. Upon moving back to Dresden for my postdoc, I continued to work on spatio-temporal organization in the groups of Christoph Weber and Frank Jülicher, where I devised and experimentally validated a theory for the motion of molecules in phase-separated systems.
What project do you plan to work on while preparing for the second funding round?
In the Hyman lab, I will take this theme in vivo and use the theoretical concepts I developed to experimentally investigate the internal structure of condensates as well as their assembly dynamics. These experiments will provide concrete directions for the next three-year funding period of SPP2191.