Proudly presenting the winners!
Jury prize: Alexander Harms, University of Copenhagen, Denmark, prize sponsored by Nikon.
Public prize: Andreas Moor, Weizmann Institute of Science, Rehovot, Israel, sponsored by the International Journal of Molecular Sciences, an open-access journal by MDPI.
Announcing our finalists of the 2018 edition of "PIs of Tomorrow"!
Dear all
We received 79 eligible (inter)national applications after the deadline. A big thanks goes to all of you for your efforts and to the evaluation committee for their tough work to select the best applications.
We're proud to present our finalists below.
Please note that all applicants are kindly invited to come to the LS2 Annual Meeting 2018 without registration fees. To make use of this offer, please register normally here and send in addition a quick mail to info@ls2.ch, so we'll cancel your automatically generated bill.
We're very much looking forward to the session!
With best wishes
The PIs of Tomorrow committee
Sponsors of the 2018 edition of the competition:
Petra Schwalie, EPF Lausanne
Single-cell RNA-seq-based Identification and Characterization of Adult Stem Cells in Adipose Tissue and Beyond
Adult stem cells (ASCs) show remarkable self-renewing, proliferative and multi-lineage differentiation capacities. As such, they are essential for tissue homeostasis and hold great promise for regenerative medicine. However, as ASCs constitute small heterogeneous populations in tissues of complex composition, their identification and characterization remains highly challenging. A good example of such unresolved cell heterogeneity is the adipose system, given the limited, and often conflicting knowledge about the identity of fat cell progenitors.
In my talk, I will discuss how we exploited the power of single-cell RNA-sequencing (scRNA-seq) to molecularly dissect the adipose stem cell-enriched fat pad (Schwalie, Dong, Zachara et al., Nature, in review). Our approach revealed a novel stromal cell population that resides within adipose tissue and negatively controls fat cell differentiation. These cells may be critical for modulating the plasticity and metabolic signature of distinct fat-cell containing systems, with implications for obesity, insulin sensitivity and diabetes. In addition, I will present a machine learning based approach leveraging on publicly available data, which accurately identifies stemlike cells de novo across various scRNA-seq dissected somatic tissues (Schwalie et al., Stem Cells, accepted). The presented findings provide a better understanding of both stem cell and adipose tissue biology and introduce novel approaches for the unbiased identification of ASCs.
Finally, I will provide an overview of my future plans, which include both (1) a fundamental research direction centered on ASC identification and characterization, and (2) a clinical one: the usage of menstrual fluid as a sample source for studying female reproductive trait disorders such as endometriosis. In this context, I have started a pilot project utilizing menstrual fluid to contrast cell composition and characteristics in endometriosis patients vs. healthy volunteers based on single-cell RNA-seq. This approach could prove transformative for the study of female reproductive trait disorders as well as our understanding of transcriptional properties of ASCs.
Tomislav Milekovic, University of Geneva
Leveraging Neuronal Ensemble Signals to Restore Movement and Communication for People with Paralysis
My goal is to develop clinically-relevant therapies based on intracortical brain-computer interfaces (iBCIs) that restore movement and independence to the paralyzed. iBCIs are neuroprostheses that use intracortically-recorded brain signals to control assistive devices or spinal and muscle stimulators that restore movements of the paralyzed limbs. Recently developed iBCI designs have brought hope for their potential to restore movement and communication, but two major obstacles prevent translating iBCIs to real-world use. Firstly, iBCIs require frequent recalibration by experts to maintain performance, thus preventing their independent use. Secondly, iBCIs have so far only restored crude, simple and slow movements. Through my research, I tackle both of these obstacles.
Previously, I developed signal processing and calibration approaches that enabled a person with locked-in syndrome to control a communication iBCI for 76 days without recalibration. I led the team that engineered and validated an iBCI that controlled spinal stimulation to restore movements of a paralyzed leg six days after spinal cord injury.
I currently work to develop an adaptive iBCI that will continuously adjust to signal changes to provide robust brain control of neuroprostheses. In parallel, I improve the brain-spine interface to alleviate gait deficits of Parkinsonian disease, resistant to all available therapies.
I plan to develop novel approaches for iBCIs that account for the disrupted somatosensory feedback leading to more comprehensive neuroprosthetic control signals. I plan to leverage these signals to restore dexterous and complex hand and arm movements to people with tetraplegia. I will validate these perspective therapies through clinical trials, and advance it towards commercialization. Therapies based on my research are ongoing clinical trials (clinicaltrials.gov/ct2/show/NCT03213561, clinicaltrials.gov/ct2/show/NCT02936453), thus providing a practical pathway towards rapid translation of future developments. My work can lead to new therapies that will improve the quality of life to millions of people with paralysis, currently without therapeutic alternatives.
Sébastien Herzig, Salk Institute for Biological Studies, La Jolla, US
Uncovering Novel Regulation of Metabolism by Energy-Sensing Signaling Pathways
My main PhD project was aimed at understanding the function of a family of uncharacterized mitochondrial proteins. We were able to discover the function of these proteins and show that they composed the long-sought-after mitochondrial pyruvate carrier. Follow up studies using mice deficient for mitochondrial pyruvate import revealed embryonic lethality that could be rescued by a ketogenic diet, highlighting the plasticity and adaptation of mitochondria to metabolic fuels. At the Salk Institute, I am working on the connections between the AMPK pathway and mitochondria. In particular, we have shown that AMPK directly phosphorylate Mitochondrial Fission Factor (MFF) to control the morphology of mitochondria during energy stress. I am now performing phosphoproteomics screen to uncover novel substrates of AMPK at the mitochondria and further our understanding of how AMPK controls mitochondrial function. In parallel, I am investigating the stress response pathways upon mitochondrial inhibition and how cells adapt to chronic mitochondrial stress.
I am now looking to setup an independent research laboratory aimed at characterizing novel mechanisms by which mitochondrial function and metabolism are regulated by energy sensing pathways such as AMPK. This will be pursued by three approaches. The first one will be to continue the effort currently underway to characterize novel substrates identified by the phospho proteomics screen to reveal novel aspects of metabolism regulated by AMPK. The second avenue will be to develop novel methods to screen for AMPK substrates based on CRISPR/Cas9-mediated endogenous gene tagging to allow for molecular biology techniques like proximity-labelling without the caveats of overexpression. The third avenue expands beyond AMPK to look at cellular signaling pathways in response to chronic mitochondrial stress such as the ones observed in models of mitochondrial diseases or chronic partial inhibition of the mitochondria. All together, these research projects will shed new light on the regulation of metabolism in response to energy stress and mitochondrial dysfunction and provide novel potential therapeutic avenues for diseases associated with mitochondrial defects.
Alexander Harms, University of Copenhagen, Denmark
Phages to the Front: Exploiting Bacterial Viruses to Control Antibiotic-Tolerant Infections
Bacterial persisters are antibiotic-tolerant cells that form through the entry into a dormant physiological state and that are considered to be main culprits behind the recalcitrance of chronic or relapsing infections. Despite decades of research, persisters have remained elusive and notoriously out of reach for available treatment options, while the molecular mechanisms underlying their antibiotic tolerance are still hotly debated in the field. I recently resolved some of these controversies when I showed that significant part of controversial literature on Escherichia coli persisters is skewed by a number of technical as well as biological artifacts.
Consequently, I propose to approach antibiotic-tolerant persisters from a genuinely new angle by leveraging the power of bacteriophages, i.e., bacterial viruses that were the key to many fundamental discoveries in the early days of molecular biology but have since faded from the spotlight. My preliminary results show that most bacteriophages cannot infect persister cells, but that a few of them can overcome the recalcitrance of persisters and kill them by direct infection. I therefore plan to let these bacteriophages guide me to Achilles’ heels of persister cells that are exploited by long-evolved bacteriophage strategies. In short, I will first screen a large collection of newly sampled bacteriophages for isolates with the ability to kill persister cells. Subsequently, I will explore the genetic basis of this fascinating trait using Mut-Seq, i.e., by comprehensively probing and quantifying this ability for all mutants of a chemically mutagenized bacteriophage pool through deep sequencing. Finally, targeted experiments will dissect the bacteriophage strategies to kill persister cells down to the level of molecular interactions between networks of host and phage factors. I anticipate that this project will uncover new Achilles’ heels of antibiotic-tolerant persisters that could be exploited for the development of new treatment options inspired by powerful bacteriophage mechanisms.
Enkelejda Miho, ETH Zurich
The Architecture of Large-Scale Antibody Repertoire Networks is Reproducible, Robust and Redundant
Humoral immunity is achieved by a vast ensemble of distinct antibody clones; however, the comprehensive architecture of an individual’s immune repertoire has remained elusive.
A historical paradigm shift enabled by high-throughput sequencing has led to a major transition from analyzing individual antibodies to capturing the entire diversity of antibody repertoires (Weinstein, Science, 2009). The big data generated from sequenced repertoires, however, introduced significant unresolved computational challenges, which limited network analysis. Consequently, to obtain the architecture of antibody repertoires requires a second paradigm shift – the unification of immunology with informatics (Kidd, Nature Immunology, 2014).
The architecture of an antibody repertoire is defined by the network similarity landscape of its sequences and reflects the spectrum of antigen binding, thereby determining immunological protection and function. We developed a novel high-performance computing software to construct for the first time large-scale networks from highthroughput sequences of entire antibody repertoires. We investigated the comprehensive similarity relation between B-cell clonal sequences up to the scale of naïve murine B-cell populations (≈106 estimated clones). More than 400 million sequences from various stages of the B-cell lineage (pre-B cells, naïve B-cells and memory plasma cells) of unimmunized and immunized cohorts were analyzed.
We discovered that the fundamental principles of antibody repertoire architecture are (i) reproducibility of network parameters cross-individuals (e.g., when responding to immunization, repertoires are scale-free networks dominated by relatively few clonal hubs which concentrate large numbers of clonal variants, reflecting clonal selection and expansion), (ii) robustness to extensive (50%) clonal deletion and (iii) redundancy in the sequence similarity space, where 1 a.a. differences between clones could predict larger sequence differences. These architectural principles serve as the blueprint for the construction of antibody repertoires, such as synthetic repertoires simulating natural immune systems, which can be used for immunotherapeutic and biomedical applications.
Andreas Moor, Weizmann Institute of Science, Rehovot, Israel
Spatial Division of Labor in the Mammalian Intestinal Epithelium
My research is focused on elaborating how single cells collaborate within tissues to achieve their common physiological functions. A thorough comprehension of these tissue components is crucial for advancing our knowledge of normal homeostasis and pathophysiology; disrupted cellular interactions can lead to decreased tissue function or even carcinogenesis. Collaboration happens not only across historically defined cell types, there is also significant heterogeneity within cell types and even within cytoplasmic compartments of polar single cells. Most of this widespread cellular heterogeneity remains hidden in established bulk analysis methods. The recent advances in single cell genomics would enable its study, yet the information of a cell’s spatial origin is usually lost during tissue dissociation.
In my postdoctoral research I have developed quantitative approaches to study cellular and subcellular heterogeneity while preserving information about the spatial tissue context. I have identified widespread intracellular division of labor across apical and basal subcellular areas in the intestinal lining and a new layer of posttranscriptional spatial genome regulation (Moor et al., Science, 2017).
My proposed research combines single cell genomics, single molecule transcript imaging and mechanistic studies in primary cultures such as intestinal organoids to characterize cellular and subcellular spatial heterogeneity across metabolically active mammalian tissues. RNA localization is tightly regulated in normal homeostasis and likely affected in intestinal pathophysiology. I will study its causative implication in carcinogenesis in APC knockout mouse models, a RNA binding protein that is mutated in 90% of all bowel cancer patients.
The results of the proposed research have the potential to reveal a previously unrecognized layer of spatial gene regulation through localized translation in mammalian epithelia. I expect that the resulting knowledge will shed light on tissue function in normal homeostasis, it could also reveal new causative disease implications and provide new therapeutic targets to tackle such mechanisms.
Confirmed jury members
We thank the jury members of the 2018 session!!
Paola Picotti (ETH Zurich)
Ioannis Xenarios (University of Geneva & Lausanne & SIB)
Michele de Palma (EPF Lausanne)
Berend Snijder (ETH Zurich)
Matthias Peter (ETH Zurich)
Dominique Soldati-Favre (University of Geneva)
Ralph Schneggenburger (EPF Lausanne)
Instructions for your application (closed now)
Dear postdocs and advanced researchers,
We are very pleased to announce the special session "PIs of tomorrow" that will be held next year at the upcoming Life Sciences Switzerland (LS2) Annual Meeting (February 12-13 2018, University of Lausanne). This session offers an opportunity to postdocs and senior researchers interested in pursuing an academic career to present a talk similar in format to a professorship application interview. A knowledgeable jury panel of professors will evaluate the presentations and provide feedback in a one-on-one session afterward.
Please refer to the attached instructions to enter the competition to be one of the five speakers selected from all applications. For the 2018 addition, one additional slot will be given to the best Postdoc talk at the Life Sciences Postdoc Day '17.
Applications must be received by November 1st, 2017.
If you are selected, your travel and accommodation fees will be paid by the LS2 organization.
Please feel free to spread the word to other potential candidates!
We are looking forward to your application and hope to welcome you in Lausanne!
Best wishes,
On behalf of the LS2 organizing committee,
Nino Nikolovski, Aleksandra Konovalova and Elisa Araldi
ETHZ AMB
www.amb.ethz.ch
and
Carolin von Schoultz
Scientific Officer LS2
www.ls2.ch
www.annual-meeting.ls2.ch
