Relevant Degree Programs
Affiliations to Research Centres, Institutes & Clusters
- Characterizing protein complexes involved in chromatin modification and epigenetic regulation
- Dissecting the regulatory mechanisms of autophagy degradation
- Investigating the molecular bases of rare diseases
Complete these steps before you reach out to a faculty member!
- Familiarize yourself with program requirements. You want to learn as much as possible from the information available to you before you reach out to a faculty member. Be sure to visit the graduate degree program listing and program-specific websites.
- Check whether the program requires you to seek commitment from a supervisor prior to submitting an application. For some programs this is an essential step while others match successful applicants with faculty members within the first year of study. This is either indicated in the program profile under "Admission Information & Requirements" - "Prepare Application" - "Supervision" or on the program website.
- Identify specific faculty members who are conducting research in your specific area of interest.
- Establish that your research interests align with the faculty member’s research interests.
- Read up on the faculty members in the program and the research being conducted in the department.
- Familiarize yourself with their work, read their recent publications and past theses/dissertations that they supervised. Be certain that their research is indeed what you are hoping to study.
- Compose an error-free and grammatically correct email addressed to your specifically targeted faculty member, and remember to use their correct titles.
- Do not send non-specific, mass emails to everyone in the department hoping for a match.
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- Highlight your achievements and why you are a top student. Faculty members receive dozens of requests from prospective students and you may have less than 30 seconds to pique someone’s interest.
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- Convey the specific ways you are a good fit for the program.
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- Be enthusiastic, but don’t overdo it.
G+PS regularly provides virtual sessions that focus on admission requirements and procedures and tips how to improve your application.
Graduate Student Supervision
Doctoral Student Supervision (Jan 2008 - Nov 2019)
No abstract available.
Post-translational modification of histones, such as the addition of acetyl groups, is a major regulatory mechanism for gene expression. Histone acetylation is catalyzed by highly conserved lysine acetyltransferase (KAT) enzymes that are often part of large, modular, and multifunctional complexes. Despite their fundamental importance, the reasons behind the tendency of these enzymes to form large complexes remain unclear. We investigated the organization of these complexes by elucidating the molecular architecture of three yeast KAT complexes: Spt-Ada-Gcn5 Acetyltransferase (SAGA), nucleosomal acetyltransferase of histone H4 (NuA4), and Elongator. The yeast SAGA complex is the largest KAT complex in yeast, and activates the expression of many stress response genes. Mutations of its human homologues have been implicated in spinocerebellar ataxia and oncogenesis. Using single particle electron microscopy and crosslinking coupled to mass spectrometry, we show that the catalytic module of SAGA resides within a highly flexible tail adjacent to numerous chromatin-binding subunits. We propose that the flexible SAGA tail is the nucleosome-interacting surface, and its plasticity serves to accommodate the various configurations of the chromatin substrate. NuA4 is another KAT complex whose catalytic subunit, Esa1, is the only essential KAT in yeast. NuA4 has highly conserved roles in the expression of housekeeping genes and the DNA damage repair pathway. Its subunits organize into modules that act independently of the complex. We show that these moonlighting modules form distinct globular structures that are peripherally associated with NuA4, which likely facilitates their dynamic nature. Similar to SAGA, NuA4 subunits that bind chromatin surrounds its catalytic subunit, possibly positioning its substrate nucleosome for efficient acetylation. Yeast Elongator, consisting of two copies each of six unique subunits, was initially characterized as a component of the elongating RNA polymerase II holoenzyme with histone acetyltransferase activity. However, further research has revealed a prominent role for the complex in modifying the wobble base pair of tRNAs. We generated the first three-dimensional reconstruction of Elongator and show that it organizes asymmetrically, with the two copies of its catalytic subunit residing in very different environments. Our structural investigations represent the first steps towards understanding the molecular mechanisms of these enigmatic complexes.
Master's Student Supervision (2010 - 2018)
In eukaryotes, autophagy is an evolutionarily conserved and essential “self-degradative” process used to maintain cellular homeostasis. Central to autophagy is the formation of double-membrane vesicles termed autophagosomes. The process of autophagosome formation is coordinated by over 35 autophagy-related (Atg) proteins. The Atg1 kinase complex constitutes one group of proteins required for the initial induction step of autophagosome formation. The Atg1 kinase complex is composed of the kinase Atg1, a regulatory phosphoprotein Atg13, and a protein scaffold Atg17 that forms a ternary complex with Atg31 and Atg29. In this study, we have determined the structure of the Saccharomyces cerevisiae Atg17-Atg31-Atg29 ternary complex by single-particle electron microscopy. The complex is an “S-shaped” dimer exhibiting an elongated architecture with an end-to-end distance of 345Å. Atg17 was found to form the central scaffold while Atg31 and Atg29 formed two globular densities tethered to the arcs formed by Atg17. Further analysis of purified Atg17 dimers showed that Atg17 mediated dimerization of the complex while Atg31 and Atg29 had a structural role in maintaining the distinct curvature of the complex. We further studied Atg1 kinase complex assembly by co-expressing a minimal pentameric assembly consisting of Atg1 CTD (residues 589-897) and Atg13 CTD (residues 384-738) with Atg17-Atg31-Atg29. Structural analysis localized Atg1 CTD and Atg13 CTD to the terminal regions of the ternary complex supporting that the N-terminus of Atg17 likely mediates complex assembly. Finally, we structurally characterized an important Atg1 kinase complex interacting partner, Atg11. Purified Atg11 exhibited an elongated architecture supporting its role as a coiled-coil protein scaffold.