Research funded by
Piazza Lab
Allosteric Proteomics
Profile
Different environmental factors such as stress, nutrients and drugs produce alterations of the chemical reactions occurring in the cells. We study the molecular interactions between small molecules and proteins as readout of the effects of the environment on biological systems. We profile this network with state-of-the-art proteomics technologies in healthy individuals and to discover what goes wrong in metabolic diseases.
Binding of small molecules to proteins can modulate the metabolic status of the cells and their gene expression dynamics. All these interaction events between protein and metabolites produce allosteric effects, which means that they regulate protein activity as a consequence of a protein structural change.
We study how cells adapt to different metabolite compounds at the molecular level, focusing on human diseases where the balance between cellular proliferation and differentiation is impaired, due to a loss of regulation of the cellular chemical reactions. Our research approach integrates multiple system biology approaches with a particular focus on novel proteomics methods, metabolomics and genomics.
For more information about our research vision and technological interest visit the laboratory website linked in the social media channels twitter and linkedIN.
Team
Group Leader
Short CV
- June 2020: Principal Investigator, Helmholtz Young Investigator,
Max Delbrück Center for Molecular Medicine, Berlin, Germany. - 2019-2020: Visiting senior scientist,
Biognosys AG, Schlieren, Switzerland. - 2014-2019: Post-Doc, Picotti lab,
ETH Zurich, Switzerland. - PhD, EMBL and University of Heidelberg, Germany.
- 2009-2014: Pre-Doc, Häring lab,
EMBL Heidelberg, Germany - 2008-2009: Research assistant,
University of Cambridge, U.K.
About Ilaria
Ilaria strongly discussing about some (most likely) scientific issue in the lab
© Sebastian Steiner (unofficial IP lab photographer)
My adventure with my scientific research seriously started with my PhD studies at EMBL in Heidelberg, There I embarked on a project studying the molecular machines regulating chromatin structure and gene expression during the cell cycle using yeast genetics, cell and structural biology. During my PhD I also stumbled into crosslinking mass spectrometry in the Beck laboratory. This brought me to study protein structures with a -omics perspective in the Picotti laboratory at ETH Zurich. There I developed a method that combines limited proteolysis and mass spectrometry to characterise interactions between proteins and metabolites (LiP-SMap, more generally known as LiP-MS). Later, I further optimised LiP-MS to discover protein drug targets on a global scale in collaboration with the proteomics company Biognosys. Now, the goal of my research as group leader is to study how metabolism regulates chromatin architecture and its impact on gene expression using proteomics, genomics and metabolomics.
Outside the lab other kinds of machines and problems bigger than mass spectrometers catch my attention. I read avidly about aviation and space exploration . My element is water, so my favorite sport is swimming.
Yun-Hsuan Huang
Short CV
Jan. 2022: PhD student, Piazza Lab, Max Delbrück Center for Molecular Medicine, Germany
Sep. 2021: MSc, Molecular Bioengineering, Technical University of Dresden, Germany
Apr. – Sep. 2021: Master’s thesis, Pisabarro Lab, Technical University of Dresden, Germany
About Yun
Yun has long been interested in protein structures and functions as she started her academic journey in biochemical science and technology. Following her interest in studying proteins, she expanded further experience in wet lab and dry lab during master. She first studied the biochemical activities of membrane proteins under different solubilization environments in Fahmy Lab of Helmholtz Zentrum Dresden Rossendorf. Then she switched to in silico side to complete the master’s thesis in Pisabarro Lab of TU Dresden. She performed structure-based virtual screening on cell cycle regulators to preliminarily filter out the candidate molecules for drug development.
Now in IP lab, she wants to explore the structures and interactions of proteins in a further global view, utilizing both experimental and computational approaches.
Music makes her day, so she plays piano and guitar often. Mountains and sea recharges her beyond the working time.
Short CV
- September 2020 – present: PhD student, Piazza laboratory.
Max Delbrück Center for Molecular Medicine, Berlin, Germany. - July 2020: Master in virology.
Charles university, Prague (Czech Republic)
About Eliška
Eliška studied molecular biology and biochemistry and continued with virology at the Charles university in Prague. Despite coming from a family of chemists, Eliška got fascinated by diseases and medicine after reading a book about ‘viruses in the 21st century’ written by her future bachelor’s thesis supervisor. She worked on the characterisation of Zika and Dengue proteases and their inhibition in the laboratory of Jan Konvalinka at IOCB in Prague. As part of her studies Eliška, also spent 7 months at Karolinska Institutet in Sweden in the laboratory of Nico Dantuma working on the inhibition of the ubiquitin-proteasome system. Now in the IPlab, Eliška wants to switch her view on the inner life of the cell and study cellular processes in a more complex, system biology-based way!
Apart from science, Eliška studied viola playing on a conservatory and played in different Czech and Swedish orchestras. Her other great passion is long-distance running and ultramarathon distance.
Claudio Bassot
Short CV
August 2021: Bioinformatician, Piazza laboratory. Max Delbrück Center for Molecular Medicine, Berlin, Germany
2017-2021: Post-Doc, Prof Arne Elofsson Group, Stockholm University, Sweden
2014-2017: PhD Student, Prof. Paolo Bernardi and Silvio Tosatto, University of Padua, Italy
2013 September: Master in Pharmaceutical Biotechnology, University of Padua, Italy
2013: Master Thesis in Erasmus, Prof. Carola Hunte Group, University of Freiburg im Breisgau, Germany
About Claudio
From his undergraduate studies, Claudio was fascinated by proteins. He had his first taste of science during his master thesis in structural biochemistry. But it was during his PhD that Claudio realized that he was more interested in tackling biochemical problems from a bioinformatics perspective and left the lab bench for the computer. Bioinformatics leads Claudio to a postdoc in Sweden at Stockholm University in the group of Prof. Arne Elofsson. There he worked with contact prediction and ab initio-protein modelling on repeats and transmembrane proteins gaining expertise in structural bioinformatics.
Now in IPlab Claudio wants to broaden his view by doing research at the proteome scale.
In his free time, Claudio likes to practice sports especially hiking, skiing and fencing and he is also passionate about history.
Short CV
June 2021: PhD student, Piazza laboratory.
2020: Master’s thesis, Küster laboratory, Technical University of Munich, Germany.
December 2020: Master in Biochemistry, Technical University of Munich, Germany.
About Maximilian
Maxi has always been fascinated by nature and the endeavor of obtaining a deeper understanding of biology. Thus, he studied biotechnology and biochemistry.
During his bachelor thesis – that he conducted in the lab of Albert Jeltsch – Maxi got interested in epigenetics. He worked on elucidating the enzymatic properties of the DNA methyltransferase 1 and is still very excited about DNA methylation today. While he pursued his master studies, Maxi took several opportunities to gain insights in different research fields: He spent half a year at the Karolinska Institute in the group of Simon Elsässer, where he used synthetic biology and MINUTE-ChIP to study the biology of the histone variant CENPA. Moreover, he carried out several short research internships in cell biology, NMR spectroscopy and chemical biology. Finally, he got especially intrigued by proteomics when he was working in the lab of Bernhard Küster for his master thesis. During the next couple of years, Maxi seeks to employ structural proteomics methods to unravel the entanglement of metabolism and gene expression.Besides science, Maxi is fond of nature in general. He likes to spend time outdoors, hiking, cycling, or searching for animals that he photographs from time to time.
The team will grow very soon… Stay tuned!
Research
OUR VISION
From a mechanistic point of view cells can be seen as integrated devices composed of a network of interactions among different macromolecules and small molecules (proteins, nucleic acids and metabolites). Most of them are protein molecular machines that carry out specific tasks, such as building structures and catalyse reactions. In our team we try to understand these complex networks and how proteins are activated. This is also important to design strategies to correct these processes when they get out of control in diseases.
During the last decade a new discipline of biology called proteomics has changed the paradigm of the methods used to study biological mechanisms. Rather than recapitulating the (bio)chemistry of single reactions reconstructed in a test tube, proteomics aims to capture a snapshot of all biological processes and molecular event occurring in vivo by profiling the levels of proteins present in the cell. Unfortunately, knowing protein abundances is not often sufficient to explain phenotypes. This is because the activity of all proteins depends not only on their abundance but also on their 3D structure. Ultimately, all factors that can modify protein’s shapes, most relevantly molecular interactions with metabolites, drugs. nucleic acids and other proteins are important for their function. Thus, a systematic and comprehensive understanding of biological processes has to take into account all these heterogenous interactions.
Probing structural states of the proteome combing limited proteolysis and mass spectrometry (LiP-MS concept).
During my post-doc in the Picotti lab and my research with the proteomics company Biognosys AG, I have further developed a method that increases our understanding of the function of proteins (LiP-MS). With LiP-MS we measure global protein structural changes of proteins by limited proteolysis (LiP) and quantitative mass spectrometric analysis of the resulting peptides.
Different kinds of cellular social interactions that can be investigated with the LiP-MS technology.
Guided by the paradigm that a change in activity generally correspond to a change in structure, this powerful techniques allows us to study protein structural changes associated to many different types of molecular cues. For instance:
- Assembly-disassembly of protein complexes
- The effects of phosphorylation on protein function
- Interactions of protein to metabolites
- Identification of protein drug targets in vitro and in vivo
- Dynamic interactions of proteins with nucleic acids
- Protein stability changes due to mutations or aggregation
We are also very interested in advancing further the field of structural systems biology by improving new structural proteomics workflows and their applications to different interactomics workflow. With the multidisciplinary research and collaborative atmosphere of the MDC, we aim to combine these state-of-the-art proteomics methods with genomics, metabolomics, stem cell biology and computational biology. Our general goal Is to advance the general knowledge of basic research and make a direct impact on topics related to human health. We are in the right environment to do so.
OUR GOALS
Different environmental cues such as stress, nutrients or drugs, trigger rapid adaptive responses that allow to maintain cellular homeostasis. One of the fastest cellular responses to the environment is the binding of small molecules to proteins. These molecular interactions produce allosteric effects, which means that they trigger a variation of protein activity as a consequence of a structural conformational changes that occurs instantly. Allosteric interactions are thus essential for life and can modulate both the metabolic status of the cells and gene expression.
We study how cells adapt to different metabolite compounds at the molecular level, focusing on the regulation of the balance between cellular proliferation and terminal differentiation in stem cells. Metabolite levels can control both the inherent proliferative properties of stem cells in normal conditions but also their uncontrolled proliferation, which may lead to diseases like cancer.
In cancer diseases leukaemia the balance between cellular proliferation and differentiation is impaired. Our team is interested in understanding how this happens at the molecular level. We will use multiple system biology approaches with a particular focus on novel proteomics methods, metabolomics and genomics to study:
- The principles and pervasiveness of metabolite regulation of chromatin.
- How metabolites control stem cells fate in leukaemia.
- How to efficiently modulate the chromatin-metabolite network with drugs.
To tackle these questions we need advanced bioinformatics and a structural-system biology prospective. We will integrate these different levels of gene regulation into predictive models that elucidate their function in collaboration with other research groups at the MDC and with the Berlin institute of medical system biology.
Publications
News
LiP technology
Here you can watch a great video about how Limited Proteolysis (LIP) works and its application for finding drug targets. Video credits; Biognosys