Open PhD Projects
 

The following PhD projects are available in 2023 (earliest possible start in May 2023):

Bartfeld Lab: Innate immune recognition in the gastrointestinal epithelium – Organoids as host model

Diefenbach Lab: Role of ILC3 and ILC3-derived effector molecules for metabolic adaptation during pregnancy

Domenech de Cellès Lab: Elucidating the impact of climate on the seasonal dynamics of respiratory viruses

Iatsenko Lab: Deciphering the mechanisms of innate immune responses using Drosophila melanogaster as a model

Key Lab: Within-person evolution of the human microbiome

Majer Lab: How endomembrane remodeling controls immune signaling from endosomes

Osterrieder Lab: Mechanisms of adaptation in proofreading impaired large DNA viruses (Co-supervision with Jakob Trimpert)

Portugal Lab: Plasmodium falciparum variant surface antigens (VSAs), antibodies and poor cytoadhesion promoting asymptomatic persistence of malaria parasites

Romagnani Lab: Adaptive NK cell responses in infections and tumors

Taylor Lab: Molecular dynamics of Innate Immune protein condensates

 


Bartfeld Lab: Innate immune recognition in the gastrointestinal epithelium – Organoids as host model

The epithelial cells of the gastrointestinal (GI) tract are in constant contact with microbial products and have to balance tolerance of commensals and defense against pathogens. To sense the microbial world, epithelial cells are equipped with innate immune receptors, such as toll like receptors or inflammasomes. Our group uses adult stem cell derived organoids to better understand epithelial innate immunity and the host response to infection. Organoids are 3-dimensional, primary cell cultures. Analyzing human and murine GI organoids, we found that innate immune receptor expression is highly organized in the GI tract: Each segment of the GI tract expresses a specific set of innate immune receptors. We now wonder, how this spatial organization develops and how this impacts the defense against pathogens. In this project, we will use CRISPR/Cas9-mediated genetic modification of human GI organoids to analyze the impact of specific genes on innate immune receptor expression. We will further use infection models, such as EPEC infection of human intestinal organoids, to better understand the importance of innate immune recognition in infection.

To find out more about the Bartfeld Lab (Institute for Medical Biotechnology, TU Berlin).


Diefenbach Lab: Role of ILC3 and ILC3-derived effector molecules for metabolic adaptation during pregnancy

Innate lymphoid cells (ILC) are tissue-resident innate lymphocytes that are involved in immunity to infections but are also deeply integrated in the regulation of tissue function. For example, our recent work revealed that ILC support nutrient uptake in the small intestine and that changes in ILC effector programs affect systemic metabolism (Gronke, Nature 2019; Guendel, Immunity 2020; Diefenbach, Immunity 2020). In this project, we are exploring the role of ILC3 and ILC3-derived effector molecules for metabolic adaptation during pregnancy. Pregnancy is one of the biggest challenges to metabolic demands in life and it constitutes a physiological state of metabolic syndrome. The role of immune system components in general and of ILC in adapting the organism to this demand is unknown. Our preliminary data indicate that pregnancy is linked to intestinal growth resulting in a larger number of enterocytes for nutrient absorption. Interestingly, mice lacking ILC3 had impaired growth of the intestinal organ and nutrient absorption was reduced resulting in lower birth weight of the offspring and reduced caloric content of breast milk. The project will address the following specific aims: (1) how do ILC3 mechanistically regulate epithelial growth; (2) which epithelial cell programs are controlled by ILC3 and (3) how do these changes affect systemic metabolism and health of the offspring?

Funding: ERC AdG, DFG

To find out more about the Diefenbach Lab (Institute of Microbiology, Charité Universitätsmedizin Berlin) .


Domenech de Cellès Lab: Elucidating the impact of climate on the seasonal dynamics of respiratory viruses

Seasonality is an intriguing aspect of many infectious diseases. These include infections caused by respiratory viruses like influenza viruses, respiratory syncytial viruses, and rhinoviruses, which collectively cause large morbidity worldwide. The incidence of these viruses is markedly seasonal in climatically diverse locations, but the mechanisms underlying these seasonal patterns remain poorly understood. Elucidating those mechanisms is essential to better understand the epidemiology of these viruses, to prepare for epidemics, and to design control strategies.

The PhD project will aim to elucidate the seasonality of respiratory viruses, in particular the impact of climatic variables—like temperature and humidity—on their transmission dynamics. The successful applicant will develop mathematical models of transmission, confronted with detailed epidemiological data using modern statistical inference techniques, to systematically assess the likelihood of different seasonal mechanisms.

Profile of candidate’s qualification:

  • M.Sc. or equivalent degree with a background in a quantitative discipline (e.g. mathematics, statistics, physics) and a keen interest in biology, epidemiology, and public health
  • candidates with experience in programming (in particular R) and with mathematic and statistical modeling will be strongly considered
  • applicants with a background in biology or medicine may also apply if they can demonstrate significant experience with quantitative approaches

To find out more about the  Domenech de Cellès Lab


Iatsenko Lab: Deciphering mechanisms of innate immune responses using Drosophila melanogaster as a model

The Iatsenko Lab at the Max Planck Institute for Infection Biology (Berlin, Germany) is looking for a motivated PhD student to study host-microbe or microbe-microbe interactions in the Drosophila model. We are seeking highly qualified and motivated applicants with strong experimental lab skills in the fields of Drosophila genetics, molecular biology, or microbiology. Candidates with interests in mechanisms of microbial pathogenesis and microbe-microbe interactions (microbiologist) or the regulation of innate immune responses (Drosophila geneticist) are encouraged to apply.

To find out more about the Iatsenko Lab


Key Lab: Within-person evolution of the human microbiome

The human microbiome describes the entirety of microbes on an individual and its establishment has important implications for human health. The human microbiome contains trillions of microbes, which harbor an enormous adaptive potential, generating millions of new mutations every day. However, we have a very limited understanding about the role of the species-specific genetic variability for colonization and perturbation of the human microbiome throughout life.

Here, we will use whole-genome sequencing of cultured bacterial isolates combined with metagenomics from individuals to reconstruct the genetic drivers behind persistent colonization and perturbations during health and disease. A better understanding of the genetic mechanisms provides the basis for the development of new strategies to support the establishment of a healthy human microbiome.

Therefore, we are looking for a motivated student to work at the interface of microbiology (incl. robotic automation) and computational genetics in our lab.

The ideal candidate has knowledge in a programming language (python, bash, R etc.) and a background in microbiology, genetics, bioinformatics, evolutionary biology or neighboring disciplines.

To find out more about the Key Lab


Majer Lab: How endomembrane remodeling controls immune signaling from endosomes

Our immune system utilizes a variety of pattern recognition receptors to detect pathogenic features and respond to infection. In my lab, we seek to understand how nucleic acid-sensing Toll-like receptors manage to successfully discriminate between foreign and self-derived DNA/RNA, in order to avoid self-recognition and autoimmunity. The key mechanism to limit self-recognition is their intracellular location within late endosomes, which are poorly accessed by host-derived nucleic acids from the extracellular space. We have recently discovered that perturbing endosome function in macrophages, through deletion of the endosomal BORC protein complex, leads to an accumulation of TLR7 within the endosomal network, shifting the receptors distribution and resulting in uncontrolled responses to RNA ligands. Multiple environmental stimuli, such as cytokine exposure, chronic inflammation, or infection induce massive endomembrane remodeling in myeloid cells. In this project we want to investigate whether such external stimuli could alter the cells endosome physiology in a way to predispose TLR7 towards self-recognition and autoimmunity. You will learn how to work with primary cell culture systems and mouse models, and use Crispr/Cas9-genome editing, advanced imaging and biochemical techniques.

To find out more about the Majer Lab


Osterrieder Lab: Mechanisms of adaptation in proofreading impaired large DNA viruses (Co-supervision with Jakob Trimpert)

Replication errors in large DNA viruses usually occur at comparatively low frequencies. Intrinsic 3’-5’ exonuclease activity of the viral DNA-polymerase enables proofreading of nascent DNA and reduces error rates during DNA replication. The separation of exonuclease and polymerase activity within the holoenzyme allows for manipulation of proofreading without impairment of polymerase activity. Consequently, mutation rates rise while efficient replication is maintained when proofreading is impaired in exonuclease deficient mutants. Increased mutation frequencies allow studying viral evolution within significantly shorter periods. Employing this system, we aim to study different aspects of viral evolution such as host adaptation, spillovers, development of antiviral resistance as well as the evolution of virulence and immune evasion. From traditional cell culture and reverse genetic systems to next generation sequencing and single cell RNA-sequencing, we will employ a wide array of techniques to characterize and understand viral adaptation in various contexts. In doing this, we aim to understand if diversity itself is a mechanism of adaptation or if only single genomes within diverse populations are selected for individual fitness. Would, in this context, unlinked mutations within a population complement each other or would they increase population-intrinsic conflict? We wonder: how social are viral populations?

To find out more about the Osterrieder Lab (Institute for Virology – FU Berlin, Department of Veterinary Medicine)


Portugal Lab: Plasmodium falciparum variant surface antigens (VSAs), antibodies and poor cytoadhesion promoting asymptomatic persistence of malaria parasites.

We have recently shown that parasites isolated during the dry season are transcriptionally distinct from those in subjects with febrile malaria in the transmission season, coinciding with longer circulation of parasitized erythrocytes within each replicative cycle that do not adhere to the vascular endothelium. We have shown that low parasite levels during the dry season are not due to impaired replication, but rather increased splenic clearance of longer-circulating infected erythrocytes (Andrade et al. 2020). These observations highlight a key role for cytoadhesion of infected reb blood cells (iRBCs) in modulating parasite growth and malaria pathology beyond the described connection with severe disease. Also, these data suggest that on the other end of the spectrum, in subclinical infections, minimal adhesion of iRBCs prevents increases in parasitaemia, thereby promoting parasite persistence.
We now seek to determine the effect of anti-VSA antibodies on VSA gene switching during the dry season, its effect on cytoadhesion, and to uncover immune targets with potential to eliminate silent reservoirs. We hypothesize that within a clonal infection, sequential presentation of VSAs on iRBCs, and a corresponding ordered acquisition of antibodies favours progressively less virulent variants. In collaboration with Prof. Boubacar Traore’s laboratory at the Malaria Research and Training Centre in Mali
 we propose to: 1. test how plasma collected throughout time recognise VSAs of parasites collected sequentially. 2. determine how plasmas collected at different timepoints in the dry and wet seasons affect endothelial adhesion. And 3. define potential targets to use in elimination strategies directed at persistent P. falciparum reservoirs.

Methods to be used: Flow cytometry, Sorting, RNA extraction, qRT-PCR, DNA and RNAseq, ELSA, bioinformatics, cell culture, molecular biology

Profile of candidate’s qualification:

  • Graduate or Master’s Degree in Biology or related areas; work practice in Plasmodium infection is desirable; as well as experience/knowledge of immunology, cell culture, q-RT PCR, bioinformatics, and statistics
  • excellent communication skills and team spirit; organizational skills and ability to keep detailed records of experiments;
  • Critical mind and enthusiasm; ability to work in multidisciplinary and multicultural teams, and motivation to travel to malaria endemic areas

To find out more about the Portugal Lab


Romagnani Lab: Adaptive NK cell responses in infections and tumors

Our group focuses on understanding the activation and differentiation signals of innate lymphoid cells (ILC), which regulate tissue homeostasis and inflammation. Natural Killer (NK) cells are an ILC subset, playing a crucial role in the early defense against intracellular pathogens, especially herpesvirus. It has been shown that during mouse and human cytomegalovirus (CMV) infection, defined NK cell subsets undergo antigen-driven expansion and persist over time, partially resembling anti-viral adaptive responses. We have demonstrated that human adaptive NKG2C+ NK cells differentially recognize distinct HCMV strains in a peptide-dependent manner, thus identifying the long sought „antigen“ inducing these expansions. Building on these findings, we now aim to combine flow cytometry, single-cell RNA-, single-cell ATAC-sequencing, as well as in vitro and in vivo functional assays already established in the lab in order to decipher the imprints CMV infection has on the NK cell repertoire and differentiation and to understand how these characteristic expansions of adaptive NK cells are induced and maintained. Moreover, we aim to optimize our newly patented peptide-based vaccine in order to expand NKG2C+ NK cells and boost their anti-viral and anti-tumor activity in vitro and in vivo. This project will enable us to gain insights on the molecular mechanisms driving adaptive properties of innate lymphocytes and to exploit their specificity to potentiate anti-viral and anti-tumor immunity.

References:

Hammer Q, Rückert T,.. and Romagnani C, Nat Immunology 2018a

Hammer Q, Rückert T and Romagnani C, Nat Immunology 2018b

Hernandez D, .. Rückert T and Romagnani C, Immunity 2021

Stehle C, Rückert T.. and Romagnani C, Nat Immunology 2021

Rückert T .. and Romagnani C, Nat Immunology, in press

To find out more about the Romagnani Lab


Taylor Lab: Molecular dynamics of Innate Immune protein condensates

The Taylor laboratory is interested in how immune cells decode chemical information. We aim to understand how immunological signaling molecules self-organize to detect and respond to the molecular signals of disease and infection. We have developed microscopy-based assays and approaches that allow us to visualize immune signalling at the single-molecule level within live cells.

We are looking for an enthusiastic and highly motivated PhD student to join our research group. The project will examine the assembly and disassembly of the Myddosome signaling network. The Myddosome is a specialized membrane-less organelle of the innate immune system. We have discovered that Myddosomes assemble and disassemble with an intricate molecular choreography. The central questions this PhD project will address are: what are the molecular mechanisms that control assembly, disassembly and signal transduction of molecular condensates in live immune cells? To address these questions we have, in collaboration. Developed a Phase Portrait analysis, an analytical technique that examines the trajectories of a dynamical system. The student will learn to apply this analysis to live cell fluorescence microscopy data that visualizes the dynamics of Myddosome condensates.

This project is a collaboration between labs based in Dresden and Abu Dhabi. The student will have the opportunity to travel to meet and work with collaborators.

This position is suited to candidates with a strong background in physics, biophysics, or biochemistry. Candidates must have strong computational and data analysis skills. Research in your Ph.D. will include (but is not limited to):

  • Cutting-edge fluorescence microscopy techniques (TIRF, confocal microscopy, and single-molecule methods, etc.)
  • Developing and applying advanced image analysis pipelines in R and Python programming languages.
  • The opportunity to work on an interdisciplinary project that combines experimental and theoretical approaches.

To find out more about the Taylor Lab

 

 

 

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