Dr Jarema Malicki

Jarema Malicki

Reader in Developmental Genetics
Department of Biomedical Science
The University of Sheffield
Firth Court
Western Bank
Sheffield S10 2TN
United Kingdom

Room: D18 Firth Court
Telephone: +44 (0) 114 222 4638
Email: j.malicki@sheffield.ac.uk

Bateson CentreCMIAD


Developmental Biology
Cell Biology and Cancer

General

Brief career history

  • 2013-present: Reader, University of Sheffield
  • 2012-present: Senior Research Fellow, University of Sheffield
  • 1996-2010: Assistant Professor, Harvard Medical School, USA
  • 1993-1996: Postdoctoral Fellow, Harvard Medical School, USA
  • 1989-1993: Yale University, USA, Ph.D.
  • 1987-1988: Bates College, USA
  • 1983-1987: Warsaw University, Poland

Research interests

Eukaryotic cilia are fascinating highly polarized cell surface features that frequently detect and/or process extracellular signals, including small molecules, light, and polypeptides. We aim to understand how signal transduction mechanisms are assembled in cilia and how they function is processes as diverse as embryonic patterning, vision, and metabolism.

The laboratory has also some interest in other aspects of cell polarity, such as membrane subcompartmentalization and organelle positioning in cell’s cytoplasm.

Professional activities

  • Reviewer for journals: Development, Developmental Cell, EMBO Journal, Human Molecular Genetics, Human Genetics, Journal of Clinical Investigation, Journal of Neuroscience, Neuron, PloS Genetics, & others.
  • Reviewer for funding bodies: Canada Foundation for Innovation (Canada), Fundação para a Ciência e a Tecnologia (Portugal), Medical Research Council (UK), Narodowe Centrum Nauki (Poland), National Institutes of Health (USA), National Science Foundation (USA), KidneyResearchUK,  Biotechnology and Biological Sciences Research Council (UK).

Full publications

Research

Ciliogenesis and Cell Polarity

Our laboratory has extensive experience in the use of both forward and reverse genetics in zebrafish. We have cloned and characterized numerous mutant loci. More recently, we have used CRISPR nucleases to mutate several groups of loci that regulate ciliogenesis. These loci include protein deacetylases, phosphoinositide metabolizing enzymes, and regulators of apico-basal cell polarity.

We use several types of microscopy to visualize cilia: conventional confocal microscopy, selective plane illumination microscopy (SPIM), and stochastic optical reconstruction microscopy (STORM).

To identify binding partners of ciliary proteins, we use tandem affinity purification (TAP) followed by mass spectrometry and yeast two-hybrid screens. We also use mass spectrometry to identify post-translational modifications, such as acetylation, on ciliary proteins.

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Funding

  • NIH
  • MRC
  • Fight for Sight
  • British Heart Foundation
Teaching

Undergraduate and postgraduate taught modules

Level 3:

  • BMS326
  • BMS349 Extended Library Project
  • BMS369 Laboratory Research Project

Masters (MSc):

  • BMS6055 Modelling Human Disease
Opportunities

Postgraduate PhD Opportunity

IMAGING LIFE BEYOND THE DIFFRACTION LIMIT OF LIGHT

Funding status: Awaiting funding decision/Possible external funding

Project Description

Ever since its invention centuries ago, light microscopy has been hampered by the diffractive properties of light, which limit resolution to ca. 200 nm. This resolution limit precludes the visualization of many subcellular structures and has been a major obstacle in the imaging of biological processes. Recent advances in fluorophore excitation methods and image processing algorithms have overcome this limitation, increasing image resolution by as much as 10 times to about 20 nm. This new form of imaging is termed super-resolution microscopy.

Super-resolution microscopy opens unprecedented opportunities. We take advantage of this approach to image subcellular structures that regulate intracellular traffic. We focus on barrier mechanisms that regulate protein movement between the cell’s cytoplasm and the cilium, a tiny subcellular compartment involved in signal detection on cell surface. The cilium is just 250 nm across and so conventional light microscopy is not suitable visualize its inner architecture. The inner components of cilia are, however, essential for the function of many cells, tissues, and organs, including sensory neurons.

As the initial step, we applied super-resolution microscopy to image cilia of a simple unicellular organism, Tetrahymena. By localizing over 30 protein epitopes, we generated a 3D model of the cilia base. As the next step, we will extend these imaging studies to vertebrate tissues, focusing on the nervous system. We will use transgenic lines that express specialized fluorescent proteins suitable for super-resolution imaging in sensory neurons of zebrafish. This will make it possible to image vital structures, such as cilia or synaptic termini, in unprecedented detail and thereby gain insight into their function. 

Keywords: Cell Biology / Development, Genetics

Contact information

For informal enquiries about the project or application process, please feel free to contact me.


For further information about this project, and how to apply, see our PhD Opportunities page:

PhD Opportunities

Selected publications

Journal articles