>> Wed 14 Mar Frank Uhlmann (Chromosome Segregation Laboratory, Cancer Research UK London Research Institute, London)

time & place: 1:30pm - Clinical Trials Unit, TM0.08, Gibbet Hill

 

...and previously

>> Wed 25 Jan Melina Schuh (MRC Laboratory of Molecular Medicine, Cambridge)

time & place: 1:30pm - Clinical Trials Unit, TM0.08, Gibbet Hill

Actin + Oocytes: Old Love - New Affairs

Intracellular transport is vital for the function, survival and architecture of every eukaryotic cell. Long-range transport in animal cells is thought to depend exclusively on microtubule tracks. This study reveals an unexpected actin-dependent but microtubule-independent mechanism for long-range transport of vesicles in mouse oocytes. Vesicles organize their own actin tracks by recruiting the actin nucleation factors Spire1, Spire2 and Formin-2, which assemble an extensive actin network from the vesicles' surfaces. The network connects the vesicles with one another and with the plasma membrane. Vesicles move directionally along these connections in a myosin-Vb-dependent manner to converge and to reach the cell surface. The overall outward-directed movement of the vesicle-actin network is driven by recruitment of vesicles to the plasma membrane in the periphery of the oocyte. Being organized in a dynamic vesicle-actin network allows vesicles to move in a local random manner and a global directed manner at the same time: they can reach any position in the cytoplasm, but also move directionally to the cell surface as a collective. Thus, collective movement within a network is a powerful and flexible mode of vesicle transport. I will also talk about the actin-dependent mechanism of asymmetric spindle positioning in mouse oocytes.

 

>> Wed 19 Jan Anna Akhmanova (Utrecht, Netherlands)

time & place: 10am - Clinical Trials Unit, TM0.08, Gibbet Hill

friends at the ends

Microtubule plus end tracking proteins (+TIPs) are a group of factors, which specifically associate with the growing microtubule ends and regulate their dynamics and interactions with various cellular structures. Recent studies showed that a sequence motif Ser-any amino acid-Ile -Pro (SxIP) embedded in a basic, serine and proline rich region can target a variety of proteins to microtubule ends by interacting with the members of End Binding (EB) family. Since this motif is relatively short, it can arise easily during evolution, and it is thus possible that multiple yet undiscovered EB-dependent +TIPs are encoded in mammalian genomes. In my talk, I will describe the results of our searches for EB-binding +TIPs by combining proteomics and bioinformatics approaches, and the known +TIP functions.

 

>> Wed 26 Oct Andreas Merdes (CNRS, Toulouse, France)

time & place: 1:30pm - Clinical Trials Unit, TM0.08, Gibbet Hill

Atomic structure of GCP4 and functional implications for microtubule nucleation

 

>> Wed 5 Oct Stephen Royle (University of Liverpool)

time & place: 1:30pm - Clinical Trials Unit, TM0.08, Gibbet Hill

Inter-microtubule bridges in kinetochore fibres of the mitotic spindle

 

 

>> Wed 28 Sep Andrew Fry (University of Leicester)

time & place: 11am - Clinical Trials Unit, TM0.08, Gibbet Hill

Centrosome regulation through the cell cycle

 

>> Wed 7 Sep Jason Swedlow (University of Dundee)

time & place: 1:30pm - Clinical Trails Unit, TM0.08, Gibbet Hill

TBC

 

>> Thur 18 Aug Julie Welburn (Welcome Trust Centre for Cell Biology)

time & place: 1pm - Clinical Trials Unit, TM0.08, Gibbet Hill, Gibbet Hill

KInetochores and molecular motors

 

>> Wed 27 Jul Jenny Ross (University of Massachusetts Amherst)

time & place: 1:30pm - Clinical Trials Unit, TM0.08, Gibbet Hill

Controlling Microtubules Through Severing

Regulation of microtubule dynamics, length, and location is essential for cell morphology, division, and migration. Microtubule-severing enzymes are ATPases that are known to remodel microtubule arrays during interphase and mitosis, in flagella and axons. Microtubule-severing enzymes remove tubulin dimers from the middle of the microtubule to cut the filament; thus, they are lattice destabilizers. We are interested in the inherent biophysical activities of these proteins, and focus on two families: katanin and fidgetin. We use two-color single molecule total internal reflection fluorescence imaging to visualize purified severing enzymes and microtubules in vitro. We find that katanin localizes to locations of severing activity including the microtubule ends to cause selective removal of terminal dimers, appearing as depolymerization. Katanin also binds to and severs at locations of lattice defects. Like katanin, we find that fidgetin can sever and depolymerize microtubules in vitro, but fidgetin's localization and activities are different from katanin.

 

>> Fri 06 May Bill Wickstead (University of Oxford)

time & place: 3pm - Clinical Trials Unit, TM08-09, Gibbet Hill

New kinesins, new functions? Examples from Kinesin-13, -16 and -17

 

>> Fri 15 Apr Mike Geeves (University of Kent)

time & place: 1pm - Clinical Trials Unit, TM08-09, Gibbet Hill

Movers, shakers and sensors: Myosin the versatile motor of the eukaryotic cell

Myosins perform a wide range of different functions in the eukaryotic cell. We know a lot about how the basic myosin molecular motor does its job but less about how it is adapted for a wide range of different function. The seminar will explore this versatility of myosin using examples from mammalian & human skeletal/cardiac myosin, Drosophila & scallop muscle myosin and human myosin I.

 

>> Wed 6 Apr Irina Kaverina (Vanderbilt University Medical Centre, Nashville TN)

time & place: 2pm - Clinical Trials Unit, TM08-09, Gibbet Hill

GOLGI/CLASP-mediated MT nucleation to the front of migrating cells: actin/microtubule crosstalk

 

>> Fri 11 Mar Massimo Antognozzi (Bristol)

time & place: 1pm - Clinical Trials Unit, TM08-09, Gibbet Hill

USE OF VERTICALLY ORIENTED MICRO-CANTILEVERS FOR THE MECHANICAL CHARACTERISATION OF MOLECULAR SYSTEMS

This year (2011) is the 25th anniversary of Gerd Binnig, Calvin Quate and Christoph Gerber invention of the Atomic Force Microscope (AFM). In this period the AFM has proven to be an incredibly effective tool for the study of molecular systems such as proteins, single molecules and nanostructures. One area where the AFM has not made particular progress is the mechanical investigation of bio-molecular motors. In this field, optical and magnetic tweezers have proven to be much more suitable tools. Here, I will present a development of the AFM where extremely compliant micro-cantilevers are mounted vertically with respect to the sample plane (Figure 1). I will show how this change in orientation, combined with a new detection system, unlocks the use of micro-fabricated sensors for the study of bio-molecular machines such as Kinesin as well as other interesting molecular systems. I will finally show the specific advantages of force-measurements performed with micro-cantilevers and some of the most promising future applications. Link to kinesin paper

 

>> Mon 28 Feb Frank Kozielski (CRUK Beatson, Glasgow)

time & place: 2pm - Clinical Trials Unit, TM08-09, Gibbet Hill

Insights into kinesin structure

 

>> Wed 9 Feb Kathryn Ayscough (Sheffield, UK)

time & place: 1pm - Clinical Trials Unit, TM08-09, Gibbet Hill

Investigating the Molecular Mechanism of Endocytosis

Endocytosis is a highly regulated and essential process in most eukaryotic cells. It is required for recycling of lipids and trafficking proteins, and for uptake or down-regulation of cell-surface receptors. During endocytosis the plasma membrane invaginates into the cell resulting in the production of a vesicle that then fuses with endosomes and enters the endolysosomal membrane system. This process involves at least 50 proteins that assemble transiently at sites on the plasma membrane. Work in the model organism S. cerevisiae has led to significant advances in our understanding of the distinct stages that take place during endocytosis in vivo. It is now widely believed that the broad stages of coat assembly (early), invagination (mid) and scission/inward movement (late) are conserved across evolution, and that in many cases direct homologues of proteins are responsible for carrying out equivalent steps in the process. In yeast, actin is critical for the endocytic process, and a framework generated by cross-linked bundles of actin must form in order to support the invagination process. We have also shown that this framework is required in yeast to support the inward movement of membrane against turgor pressure. More recently we have investigated the role of novel actin binding proteins and a yeast dynamin in early and late stages of the endocytic process.

 

>> Mon 22 Nov Hauke Drechsler (Heidelberg, Germany)

time & place: 1pm - Clinical Trials Unit, TM08-09, Gibbet Hill

phospho-regulation of the budding yeast kinesin Kip2

 

>> Fri 12 Nov Nasir Rajpoot (Computational Biology and Bioimaging Group)

time & place: 2pm - Clinical Trials Unit, TM08-09, Gibbet Hill

TBC

 

>>Sept 27 Cornelia Wandke (Innsbruck, Austria)

time & place: 2pm - Clinical Trials Unit, TM08-09, Gibbet Hill

Human chromokinesin functions in mitosis.

 

>> Sept 3 Clarie Friel (MPI-Dresden, Germany)

time & place: 1pm - Medical School Building, A042, Gibbet Hill

Mechanism of Microtubule Depolymerisation by Kinesin-family Motor Proteins

 

>> July 21 Marcus Braun (MPI-Dresden, Germany)

time & place: 2pm - Clinical Trials Unit, TM08-09, Gibbet Hill

Ase1 brakes kinesin-14-driven inter-microtubule sliding and stabilizes bipolar overlaps

Spatiotemporal self-organization of the microtubular cytoskeleton involves motorized inter-microtubule sliding. An important example is the mitotic cell division where in the central spindle motor proteins of the kinesin-5 and -14 families cross-link and slide anti-parallel microtubules relative to each other. In vitro reconstituted kinesin-5 and -14 motorized sliding continues until microtubules separate. In cells however, stable zones of overlap are formed between the ends of anti-parallel microtubules. This process requires non-motor microtubule cross-linkers of the Ase1/PRC1/M AP65 family, which are thought to counteract motorized sliding via protein friction....

 

>> June 16 Stan Burgess (Astbury Centre, University of Leeds)

time & place: 2pm - Clinical Trials Unit, Gibbet Hill

The dynein motor comes out of the cold - electron microscopy studies of an enigmatic motor protein

Dynein We are using electron microscopy (EM), including cryo-EM and single particle 3D reconstruction, to investigate the structure and mechanism of the Dynein motor protein. From these results we propose that ATP-dependent movement of the linker during dynein’s powerstroke involves a structural change within the linker itself rather than a rigid-body rotation of the entire linker.