Alex Zwetsloot
Welcome. My name is Alex Zwetsloot. I am a Medical Research Council funded PhD. student in Anne Straube's lab, where we are interested in how the cell's skeleton is used for trafficking of cargoes as well as for cell morphology.
My project focuses on a pair of molecular motors, dynein which travels towards the minus-end of microtubules, and the kinesin-3 Kif1C which travels towards the plus-end of microtubules. Despite the fact these motors strongly prefer to travel in opposite directions, they seemingly rely on one another for bi-directional transport, and inhibiting one reduces transport in both directions. We want to understand this process and challenge the dogma that this behaviour arises from a tug-of-war between opposite polarity motors.
To address these problems, we employ a multi-faceted interdisciplinary approach, using:
- Live-cell fluorescence microscopy
- In vitro reconstitution of molecular motors and microtubules
- Simulation of bi-directional transport based upon empirical observations.
Current Research
Sept. 17 - Sept. 20: PhD. project - Bidirectional transport along microtubules: cooperation of Kif1C and dynein
A continuation of the project listed below. More details to follow.
June 17 - Sept. 17: MSc. project - Bidirectional transport along microtubules: cooperation of Kif1C and dynein, Anne Straube
Investigated bi-directional transport of vesicular cargoes (integrin-GFP, NPY-RFP) in live cells. We used the drug Ciliobrevin D or RNA interference to selectively inhibit dynein or Kif1C, tracking vesicles to quantify the effect of motor inhibition or depletion on bidirectional transport. Separately, we made insect-cell expression vectors to produce a speculative Kif1C-dynein adaptor, BICDR1, and started to establish and purify this protein from SF9 cells for use in in vitro reconstitution experiments.
April 17 - June 17: MSc. project - Developing Software and Protocols for Tiled STORM Imaging, Nick Carter
Helped to develop the Warwick Open-Source Microscope's front-end Windows 10 software for microscope image acquisition. Written in C#.NET, the software provides a graphical interface for the WOSM-TIRF, coupling the activities of the Andor iXon EMCCD Camera to those of the WOSM custom microcontroller. This software aimed to rapidly explore the full extent of the piezoelectric stage, while tiling a large-scale image for quick and easy sample finding. The final goal to create full-stage super-resolution images stitched together, and unfinalised code is now in place.
Academic History
2017-Now PhD. Interdisciplinary Biomedical Research, University of Warwick
2016-2017 MSc. Interdisciplinary Biomedical Research, University of Warwick
Completed masters section of the MRC DTP (1+3) programme with a distinction. During this year we learned about advanced microscopy, statistics, programming, molecular dynamics simulations and physical biology. We also undertook two separate three-month projects which I have summarised in Current Research.
2013-2016 BSc. (Hons) Biochemistry and Molecular Medicine, First Class, University of Nottingham
Studied many aspects of modern biochemistry and pharmaceuticals, including specialist modules in signal transduction, cancer, traffic and transport.
I undertook my final year research project in Dr Claire Friel's laboratory where I studied the role of the anti-apoptotic protein survivin in reducing microtubule dynamics. During this project I gained skills in molecular biology and protein expression, while also using techniques like single particle microscopy and microtubule cosedimentation.
