Dr Egbert Hoiczyk

Room: F21
0114 222 2733


Career History

  • 2015 - present: Senior Lecturer Dept. of Molecular Biology and Biotechnology, The University of Sheffield.
  • 2002 - 2015: Assistant Professor, Dept. Molecular Microbiology and Immunology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD, USA.
  • 1998 - 2002: Postdoctoral Fellow, The Rockefeller University, New York, NY, USA.
  • 1997 - 1998: Postdoctoral Fellow, Max von Pettenkofer Institute, Munich, Germany.

Honours and Distinctions

  • 2005: Faculty Innovation Award (Dept. of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University)
  • 2000 - 2002: Howard Hughes Medical Institute (HHMI) Fellowship
  • Since 1992: Permanent Member of the German National Scholarship Foundation1986-1989 Student Fellowship of the German National Scholarship Foundation (“Studienstiftung des Deutschen Volkes”)
  • 1990 - 1992: PhD Fellowship of the German National Scholarship Foundation

Research Keywords

Microbiology, structural biology, ultra-structure, cytoskeleton, motility, nano-organelles


My laboratory uses high-resolution light and electron microscopy to study the structure, dynamics, and functions of important bacterial subcellular complexes to determine how they contribute to cellular organization.

Recent advances in high-resolution microscopy, bioinformatics, and structural determination have resulted in a fundamental reassessment of bacterial cell organization. Once perceived as simple and unorganized, in recent years bacteria have become appreciated for possessing structural, spatial, and temporal organizations that rival that of eukaryotic cells. Through an approach that couples advanced microscopy with classical genetics, biochemistry, and cell physiology, we aim at understanding how this complex organization is achieved and maintained in cells. Two different experimental approaches are used to accomplish this goal. The first approach relies on the fractionation of cells to discover, isolate, and characterize novel sub-cellular complexes and organelles that form the elementary building blocks of bacterial cells, while the second approach uses live imaging techniques, electron tomography, and genetic studies to study the function and dynamics of these structures in the context of living cells.

For most of our work, we use the predatory soil bacterium Myxococcus xanthus as model organism. M. xanthus is highly social and forms large multicellular swarms that cooperatively feed on organic matter, including other bacterial cells, which are digested through the secretion of lytic enzymes [Fig. 1]. With a nearly 10 MB genome containing 7500 ORFs and a complex life-cycle that includes cellular differentiation, M. xanthus offers excellent opportunities to study bacterial cellular organization on a cellular level, and the contributions of the organelles to cellular differentiation processes and multicellular behaviours. To complement these studies we occasionally use additional prokaryotic organisms, including cyanobacteria and archaea that help validate and expand our findings in myxobacteria.


Figure 1: The social soil bacterium Myxococcus xanthus is characterized by a complex life cycle. Vegetative cells grow and divide until starvation leads to the aggregation of about 105 cells, which form small haystack-shaped mounds that eventually develop into mature macroscopic fruiting bodies. During this process about 20% of the aggregated cells differentiate into myxospores, while 75% of the cells die, and 5% become peripheral rods, specialized cells that continue to search for food outside of the fruiting body. Exposure to nutrients will eventually result in the germination of the myxospores and re-emergence of vegetative cells forming swarms. Figure reproduced from Nat. Rev. Microbiol 2007 5: 862-872.

Currently, we are working in the laboratory on the following three cellular structures, focusing both on their structures and their functions, and potential interactions with each other:

1.) Novel bacterial cytoskeleton proteins
2.) Molecular motors of gliding bacteria
3.) Bacterial nano-organelles

1.) Novel bacterial cytoskeleton proteins
Recent genetic and cytological research has identified a number of highly important cytoskeleton proteins in bacteria, including those that are homologs to eukaryotic tubulin (FtsZ), actin (MreB), and intermediate filaments (crescentin). A more recent addition to the growing number of bacterial cytoskeleton elements is bactofilin (1). Bactofilins are a highly conserved family of proteins with a widespread distribution that are important for many fundamental cellular processes such as growth, cell shape maintenance, polarity, and antibiotic resistance [Fig. 2].

fig2Figure 2: In Myxococcus xanthus, BacM, one of four bactofilins, is morphogenic (upper row) and contributes to antibiotic resistance (middle row) and osmotic tolerance (lower row).

Research on various bactofilins has shown that these proteins are tripartite possessing short variable N- and C-termini that flank the central highly conserved bactofilin domain. This domain is formed by a beta-strand solenoid that robustly polymerizes in an end-to-end fashion (2) in the absence of cofactors into thin ca. 3 nm wide filaments [Fig. 3 and movie 1].

fig3Figure 3: Isolated native BacM fibres are higher ordered structures (A) that are formed by thinner ca. 3 nm filaments (white triangle in panel B) that can occasionally be observed exiting a fibre bundle. C) Inside the living cell BacM forms a cell-spanning cytoskeleton that can be visualized using fluorescent light microscopy.

While certain buffer conditions allow the isolation of these filaments, it appears that under physiological conditions they bundle into higher ordered fibres. These fibres appear to be the elementary structural form of BacM inside living cells, which at high protein concentrations can continue to assemble into thicker bundle-shaped rods (1). Currently, many structural and functional aspects of bactofilins are unsolved. For example, in some species it has been found that mature polymerized bactofilins are proteolytically processed at the N-terminus, suggesting that posttranslational modification may play an important role in the control of polymerization (1). Moreover, although peptidoglycan-modifying enzymes have been found to interact with bactofilins in certain bacteria, which may represent the output modules of bactofilins in these species, no such enzymes have so far been identified in M. xanthus, leaving the question open how bactofilins exert their influence.
Our current research on bactofilins focuses on the following three areas: a) To understand how individual bactofilin molecules polymerize into filaments, fibres, and eventually a cell-spanning cytoskeleton; b) To identify proteins that interact with the various structural forms of bactofilin and to understand how bactofilin contributes to their functions; and c) To elucidate the dynamics of the bactofilin cytoskeleton in living cells during vegetative growth and cellular differentiation.

2) Molecular motors of gliding bacteria
Motility is paramount for all aspects of the M. xanthus life cycle: swarming, hunting, and aggregating (3). Therefore, perhaps not too surprisingly, the cells have developed two independent motor systems, termed A (adventurous) and S (social), to power their surface-associated movements. The S-motor has been identified as type IV pili; molecular grappling hooks that extend, attach, and retract, thereby pulling cells forward. The identity of the A-motor is currently uncertain. Although no consensus for the nature of the A-motor has so far emerged, important behavioural, molecular, and genetic observations have yielded three A-motility models [Fig. 4]:


Figure 4: The three current models for A-motility: a) Focal adhesions push the cells forward by moving backwards along a cytoplasmic track; b) deformations of the outer membrane by high-drag cargo push against secreted slime; and c) secretion and expansion of a gel-like slime propels the cells forward (see text for details).

The focal adhesion model (a) suggests that extracellular focal adhesions attach the cell to its substratum at fixed positions. This model posits foci that originate at the leading pole and are connected through a multi-protein complex to the inner membrane motor proteins that traverse a helical cytoskeleton track. Their movement along this track should generate the necessary propulsive force in a direction opposite the movement of the motor against the track. According to the helical rotor model (b), A-motility is the result of the transport of high- and low-drag cargo protein complexes along closed-loop helical cytoskeleton tracks. Because of their size, the high-drag cargos deform the outer membrane moving the cells forwards while pushing against the extracellular substrate, forming punctae that resemble focal adhesions. Finally, the slime extrusion model (c) postulates that motility is the result of the secretion and expansion of a gel-like slime from nano-molecular nozzle complexes that are located in the outer membrane of the cells. Once the slime attaches to the substrate, further secretion and swelling will push the cells into the opposite direction (3-5).
Current research in the laboratory focuses on the isolation and identification of the protein components of the slime nozzle [Fig. 5].

fig5Figure 5: Electron micrograph of negatively stained isolated slime nozzles. The nozzle organelle has bilateral symmetry and has an opening at the end of 6-8 nm, which is clearly visible in the averaged side-views of the organelle (shown in the inset).

Preliminary experiments have identified the principal component of the slime nozzle, and deletion of the gene encoding the nozzle protein results in cells deficient in A-motility. These observations confirm that the nozzle protein is an essential part of the A-motility machinery and that slime secretion is necessary for this type of motility. Further research will focus on the identification of additional nozzle-associated proteins as well as the question of whether slime secretion provides the physical force for motility or instead only passively contributes to the process by facilitating the contact to the substrate.

3.) Bacterial nano-organelles
For many years, it was thought that the absence of intracellular organelles was a defining organizational characteristic of prokaryotic cells. Intriguingly, this misconception arose despite the fact that exceptionally large bacterial organelles, such as the carboxysomes, were among the first structures discovered by light microscopy inside bacterial cells. Only recently, however, research has revealed that bacteria contain a multitude of organelles, albeit most too small to be visualized by conventional light microscopy. What all bacterial organelles have in common is that, in contrast to their eukaryotic counterparts, protein shells enclose them rather than membranes.
One such recently described organelle is encapsulin (6, 7), an iron-storage organelle that possesses a protein shell containing the HK97 fold, a structural motif widespread among virus capsids, including the capsid of herpes viruses. Inside their protein shells, encapsulins from M. xanthus contain at least three small proteins, two of which contain iron-binding motifs and share similarities with ferritins (7). During vegetative growth, M. xanthus cells synthesize the shell protein EncA but do not assemble the small protein-containing holo-organelles. This assembly is initiated upon starvation (Fig. 6), the key signal that initiates M. xanthus cell aggregation (Fig. 1). During assembly, the encapsulin holo-organelles are loaded with iron, forming ~14 5-6 nm wide spherical granules inside the EncA protein shell (Movie 2). Physiologically, the concomitant removal and storage of large amounts of iron (totalling about 30,000 iron atoms per nanocompartment) helps to protect the cells from oxidative damage.


Figure 6: A) EM of negatively stained purified encapsulins showing their spherical virus capsid-like structure. Scale bar, 100 nm. B) SDS-PAGE of purified encapsulins reveals the abundant outer shell protein EncA as well as the three minor proteins found in the interior of the holo-organelle (EncB, C, and D). C) Atomic model of the T=3 EncA capsid based on cryo-EM preparations. Scale bar, 5 nm.

Our current research on the function of encapsulin in iron sequestration focuses on the following areas of research: a) to understand the structure of the encapsulin holo-organelles at atomic resolution; b) to elucidate the processes with which iron is loaded and removed from the compartments; and c) to determine what role encapsulins play in the global iron metabolism of the cell.


Level 2 Modules

Level 1 Modules

PhD Opportunities

I welcome applications from self-funded prospective home and international PhD students; see examples of possible projects below.

You can apply for a PhD position in MBB here.

Contact me at e.hoiczyk@sheffield.ac.uk for further information.

Bactofilins and the bacterial cytoskeleton

Newly developed light and electron microscopy methods are revolutionising our understanding of bacterial cells. Once thought to be simple, bacteria have now been recognised at highly organised cells using many elements previously only known from eukaryotes. One such element is the bacterial cytoskeleton. We study bactofilins, a novel class of cytoskeleton elements involved in cell shape maintenance, cell division, polarity determination, and antibiotic resistance (see Mol. Microbiol. 2011; 80:1031-1051). The project comprises the structural and biochemical characterisation of bactofilins, the study of the numerous proteins binding to bactofilin as well as the cellular phenomena controlled by bactofilins. Depending on the interest and background of the student the project can be modified and can be more of a molecular biology project involving genetic (cloning, construction of deletions, etc.) or biochemical techniques (protein purification, protein-protein interactions, etc.) or more of a structural project involving various microscopic techniques (super resolution microscopy of the cytoskeleton, localisation studies, electron microscopy, etc.). Moreover, these aspects are not mutually exclusive.

Gliding motility in bacteria Motility is important for bacterial survival and facilitates colonisation and dispersal of bacteria. While swimming and type IV pili-based swarming is relatively well understood, gliding or adventurous motility, a form of surface-associated motility is still enigmatic. Gliding myxobacteria leave like most gliders a trail of slime behind that plays an important role in motility. The project involves the characterisation (super resolution light microscopy and cryo-electron microscopy as well protein biochemistry using pull-downs, cross linking etc.) of a recently discovered novel secretory organelle, the nozzle that appears to be the molecular motor involved in slime secretion and gliding motility (see Curr. Biol. 2002; 12:369-377). In addition, we plan to isolate the slime material and characterise its chemical composition and structure as well as characterise its secretion in vivo using novel fluorescent probes and high-resolution light microscopy techniques. Together these experiments should for the first time allow us to understand the molecular basis of gliding motility, a phenomenon that is widespread among bacteria. Again, this project can be modified depending on the interest and background of the candidate.

Selected Publications

Journal articles

Conference proceedings papers