Azkia Khan - PhD
Mitochondria are responsible for the generation of energy and ATP synthesis. Many of the mitochondrial proteins are encoded by nuclear DNA and are transported to mitochondria from cytosol. Lack of protein import causes cellular toxicity due to accumulation of non-imported mitochondrial precursor proteins leading to mitochondrial dysfunction which has been associated with many age-related and metabolic diseases.
I am working on the mitochondrial morphological changes associated with protein import deficiency. To achieve this, I am using different approaches to block mitochondrial protein import in yeast. Moreover, I am also interested to see the changes in yeast mitochondria by expressing Sars-Cov-2 protein Orf9b, which is one of the highly expressed proteins following infection and is known to bind mitochondrial surface blocking many of its vital processes. Additionally, I am working on yeast progeny tracking to determine whether these mitochondrial stress-related alterations are passed on to the progeny or not. My objective is to create a software (in collaboration with DFKI), for yeast progeny tracking using live cell imaging and AI which will then enable us to uncover disease-related inheritance patterns.
Lea Bertgen- PhD Student
Most of the mitochondrial proteins are synthesized in the cytosol and are subsequently imported into mitochondria. However due to their a-proteobacterial origin, mitochondria retained a small part of their original genome, which in Saccharomyces cerevisiae encodes for eight proteins. Seven of these are hydrophobic membrane proteins and one is a soluble mitoribosomal protein named Var1. This protein of the small mitoribosomal subunit is conserved throughout all domains of live and homologs can either be found on the mitochondrial- or nuclear genome. While metazoans relocated the gene to the nucleus, most fungi and plants maintained the gene in mitochondria. Var1 is an aggregation prone protein that requires assistance of chaperones like the mitochondrial Hsp70 and Hsp60 to keep it in a soluble state and competent to assemble into the mitochondrial ribosome.
I want to elucidate the role of Var1 in mitochondrial ribosome assembly and characterize the specific function of the mitochondrial chaperone system in this process.
Christian Koch- PhD Student
Most mitochondrial proteins are synthesized in the cytosol and are subsequently transported to the mitochondrial import machinery. However some precursor proteins associate with the ER surface before they reach their final destination. In recent years, it has become apparent that close cooperation and coordination of organelles in form of membrane contact sites (MCS) is vital for proper cellular function. The best studied MCS to date is ERMES a protein complex that connects the ER to mitochondria. The aim of my work is to elucidate the function of ERMES in the context of mitochondrial protein biogenesis and in particular the role it might play in the transfer of proteins from the ER to mitochondria.
Tamara Flohr - PhD Student
Proteins of the mitochondrial matrix are typically synthesized with matrix-targeting sequences (MTS) which direct them from the cytosol into the matrix. Surprisingly, many proteins of the mitochondrial ribosome lack such sequences. One of these proteins is Mrp17, a mitoribosomal protein of the small subunit. The protein is synthesized on cytosolic ribosomes, imported into the mitochondrial matrix and finally assembles into the Mitoribosome. Although Mrp17 has no presequence, the protein is imported very efficiently. The focus of my study is to investigate the motives that direct the protein into the matrix and identify the components that mediate the import reaction.
Saskia Rödl - PhD Student
Yeast can produce energy either by respiration or fermentation, depending on the carbon source availability. Changing the carbon source causes a variety of changes in the cells, including protein expression and degradation. So far, there is much known about cellular adaptations to respiratory growth conditions but not vice versa. In this context my study will focus on cellular modulations caused by changing growth conditions from respiration to fermentation. I’m particularly interested in glucose-induced protein degradation and its connection to the regulation of mitochondrial biogenesis.
Büsra Kizmaz - PhD Student
Mitochondria are essential organelles of eukaryotes and play important roles in metabolism and signaling. Their function depends largely on a continuous flux of metabolites, nucleotides, and cofactors into and out of the organelle. Members of the mitochondrial carrier family facilitate the transport of a variety of metabolites through the inner membrane. These carrier proteins in turn need to be expressed and translocated to the inner mitochondrial membrane to fulfill their function. The aim of my study is to elucidate the cytosolic targeting of carrier proteins and their translocation through the outer mitochondrial membrane and a distinct translocase of the inner membrane, the TIM22 complex.
Nikita Gupta - PhD Student
Most of the mitochondrial proteins are synthesized in the cytosol and are translocated to mitochondria via the mitochondrial import machinery. However, under import failure, the non-imported mitochondrial precursor proteins get accumulated in many regions of the cell, with the nucleus being one of the key locations for quality control. Still, it remains unclear what drives these non-imported mitochondrial precursor proteins to various locations and whether these mitoproteins exhibit any metabolic or regulatory functions at these destinations. In this regard, I want to elucidate the role of non-imported mitochondrial proteins in the nucleus as well as the mechanisms which drives these proteins to the nucleus.
Svenja Lenhard - PhD Student
Mitochondria consist of many hundreds of different proteins that are synthesized on cytosolic ribosomes. Mechanisms of protein translocation into these organelles have been intensively studied as they are essential for cellular function in eukaryotes. Precursor proteins can reach the inside of mitochondria either after their complete synthesis (post-translational) or simultaneous to their synthesis (co-translational). Although the import across the outer and inner mitochondrial membrane is well characterized, the processes occurring right before the translocation of a polypeptide remain unclear. Therefore, the aim of my work is to better understand how different precursors are sequestered to the mitochondrial surface and what determines post- or co-translational import.
Pavel Simakin - PhD Student
Modular Cloning (MoClo) allows the combinatorial assembly of plasmids from standardized genetic parts. It is a very powerful strategy which enables highly flexible expression patterns without the need of repetitive cloning procedures. In this study, I enlarged the yeast toolkit and added sequence parts for the reliable intracellular targeting of proteins. The results appeared to be highly promising since as the MoClo approach allows it to optimize protein expression by finding the perfect combination of promoters, targeting sequences, epitope tags and vector backbones in simple, multiplexed approaches.
Anna-Lena Ecker - PhD Student
Mitochondria are essential organelles of eukaryotic cells. As a relic of their a-proteobacterial origin, mitochondria still contain a small genome. In S. cerevisiae, the mitochondrial genome encodes for seven hydrophobic subunits of the respiratory chain and a ribosomal protein. However, in order to fulfill the multitude of mitochondrial functions, more than 900 mitoproteins are nuclear encoded, cytosolically translated and subsequently imported into mitochondria.
The main question of my study is to find out why not all mitochondrial proteins have been transferred to the nuclear genome. Therefore, the aim of my project is to investigate if it is possible to cytosolically express hydrophobic mitochondrial encoded proteins, mainly Cox2, Cox3 and Atp6, and subsequently target and import them into mitochondria.
Quantitative Cell Biology group
Our group uses high-throughput genetics, microscopy and biochemistry to understand the coordination between protein translation and protein import into mitochondria. Most of mitochondrial proteins are translated on cytosolic ribosomes, complicated and ancient molecular machines. Many mitochondrial proteins are made in the cytosol, far away from mitochondria, and spend some time there before being imported. Other mitochondrial proteins are translated in close proximity to mitochondrial membrane. Why does it happen? How the fate of each protein is determined? What are the factors that regulate translation in the proximity of mitochondria? How deep does local organization of translation go next to organelle membranes and organelle subdomains? To answer these questions, we use the power of yeast genetics. In this organism, we can easily modify each gene and create custom collections of mutants that span the whole genome. Manipulating these collections in parallel we can study multiple proteins simultaneously, quantitatively compare them to each other and discover pathways that govern their import.
Yury Bykov - PhD
Tel.: +49 (0)631-205-2885
- 2023-present – Group leader in Cell Biology Department
- 2018-2023 – Postdoc, Weizmann Institute of Science (lab of Maya Schuldiner)
- 2013-2018 – PhD, European Molecular Biology Laboratory (lab of John Briggs)
- 2008-2013 – Diploma in Biochemistry, Moscow State University
Gülsah Göktas - Master Student
Tel.: +49 (0)631-205-2409
Gülsah is developing a reporter to measure the number of ribosomes in the proximity of mitochondrial membrane in living cells. Does this number change in different growth conditions, or cells keep it stable? What happens if the number of ribosomes on the outer membrane is perturbed? What are the translation quality control factors next to the outer membrane? These are some of the interesting questions she tries to answer using different reporters.