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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

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.

 

PhD Student

 

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.

 

Technical Assistant

 

Short CV

  • August 2020 – present: Technical Assistant, Piazza laboratory.
    Max Delbrück Center for Molecular Medicine, Berlin, Germany.

About Katrin

Katrin has been working since 2005 at the MDC in the Lipp and Jentsch groups. Katrin is making sure that everything in the laboratory is up and running and welcomes newcomers in the group. Currently, this is more like helping Ilaria building the lab and ordering shiny new equipment and supplies!

 

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:

  1. The principles and pervasiveness of metabolite regulation of chromatin.
  2. How metabolites control stem cells fate in leukaemia.
  3. 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

© Biognosys
Biognosys website https://www.biognosys.com

Here you can watch a great video about how Limited Proteolysis (LIP) works and its application for finding drug targets. Video credits; Biognosys

Ilaria Piazza
Dr. Ilaria Piazza
Group Leader
Contact
Max-Delbrück-Centrum für Molekulare Medizin (MDC)
Robert-Rössle-Str. 10
13092 Berlin, Germany
31.1: Hochbau
Raum 3001
 
 
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Research funded by

ERC - European Research Council (logo)
Helmholtz Association (logo)