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 Member Staff Logo


CMIAD Logo

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.

banner

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

1. Imaging life beyond the diffraction limit of light

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 using light microscopy and has been a major obstacle in the imaging of biological processes.  Recently, 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 for imaging biological structures.  We take advantage of this approach to image subcellular structures that regulate intracellular traffic.  We focus on a barrier structure that regulates protein movement between the cell’s cytoplasm and the cilium, a tiny subcellular compartment on the surface of cell.  The cilium is just 250 nm across and so conventional light microscopy cannot be used to visualize its inner architecture.  The inner components of cilia are, however, essential for the function of many cells, tissues, and organs.

We have recently obtained excellent quality super-resolution images in a simple unicellular organism, Tetrahymena.  The purpose of this project is to extend these imaging studies to vertebrate tissues, focusing on the nervous system.  To this end, we will use transgenic lines that express specialized fluorescent proteins suitable for super-resolution imaging in sensory neurons.  This will make it possible to image vital structures of these neurons, such as cilia or synaptic termini, in unprecedented detail and thereby gain insight into the function of these cells.


2. The Role of cilia in processing of visual information

Supervisors:

Neurons of the vertebrate central nervous system, including these in the hippocampus and the cerebral cortex, are ciliated.  The function of these neuronal cilia remains, however, a mystery.  It is currently believed that central nervous system cilia may contribute to higher brain functions, such as memory and their malfunction may lead to psychiatric disorders, including schizophrenia and autism.

The proposed project will investigate the role of cilia in the processing of visual information in the retina using the zebrafish model. A combination of state-of-the-art techniques, including molecular genetics and 2-photon imaging of neuronal activity, will be used to study how the activity of visual neurons is affected by mutation causing abnormal ciliogenesis.

Keywords: Molecular Biology, Neuroscience/Neurology

For informal enquiries about this project, please contact:

For further information about these projects, and how to apply, see our PhD Opportunities page:

PhD Opportunities

Selected publications

Journal articles