About Jon (For Grown-ups)

About Jon (For Grown-ups)

Overview

I do research in physical organic chemistry, and taught at university and high-school levels.  This page describes the professional side of me.  My current CV can be found at the end of the page.

I welcome employment possibilities, but I will be traveling and spending some time with my folks in Hong Kong.  That said, if you have interesting work for me starting March 2012 or after, you should definitely give me a shout!  J

Research

The membrane is the city wall of a cell, preventing what is on the outside from coming inside.   Ion channels are its gates and gatekeeper, selectively letting through just the right entities at the right situations.  The opening and closing of these molecular machines are responsible for our rhythmic heartbeats, electrical signal in neurons, and indeed, the computer between our ears.

My dissertation continues on a long line of inquiry that began with, “Natural channels are great – but can we craft ion channels from scratch?  Can we understand how they work?”  If we can, then it is possible to tailor ion-channels for technological and perhaps medical functions.  The answer to the first question is an unambiguous Yes – I found quite early that we can indeed make ion channels from simple, basic components.  The answer to the second question is more complex and nuanced, the development of which are captured in the following papers and the dissertation (for which a condensed comic form is available here).

Highlights

Ionic conductance of synthetic channels: analysis, lessons, and recommendations

A New Method for Representing Voltage-Clamp Data
[one_half][quote]The authors have brought together the massive and varied work done over the past 3 decades on synthetic ion channels. They provide us with a chemically intuitive way to better understand the activity of these many varied conducting compounds.  […] This review is going to be required reading by all in my group and I can’t wait to go back and read it again myself. Overall, an extremely well-organized and well-written review that will be useful and stimulating for both the novice and the more experienced researchers in the field.[/quote][/one_half] [one_half_last][quote]An innovative method is proposed to order the available material and possibly extract new hints or more.  The excellent data collection represents a heroic effort, the analysis provided and conclusions drawn are of outstanding originality and lucidity. […] This is a masterpiece, a result of many years of experience.  It will make an impact, the community will appreciate, should be published with high visibility.[/quote][/one_half_last]

Summary. Synthetic ion channels have been known for nearly three decades, but it is only in the past decade that analysis of the currents these ionic conductors carry has become a standard technique. A broad range of structural types have been explored and these reports have produced a very diverse collection of ion channel conductance behaviours. In this critical review we describe a notational method to extract salient information from reported ion channel experiments. We use an activity grid to represent quantitative information on conductance and opening duration with a five-level colour code to represent qualitative information on the nature of the conductance–time profile. Analysis of the cumulative dataset suggests that the reported conductance data can reflect the structural features of the compounds prepared, but does also reflect the energetic landscape of the bilayer membrane in which synthetic ion channels function.  [Link]

Apparent fractal distribution of open durations in cyclodextrin-based ion channels

Power-law Distributed Ion Channel Activities

[one_half][quote]This is outstanding work, original, innovative, thoughtful, broad-minded, provocative, delightful to read, probably controversial, certainly thought-provoking, just how great science always should be.  The manuscript should be published with highest priority.[/quote][/one_half]

[one_half_last][quote]The ideas and the statistical analysis put forward here should help the ion transport community recognize that 1) things aren’t always well-behaved with simple open and closed cases and 2) there may really be some gold nuggets in that strange looking data that many of us often obtain (more often than what is reported that’s for certain). After reading this paper I want to go re-evaluate some of the data that we never knew how to deal with..[/quote][/one_half_last]

Summary.  Cyclodextrin-based ion channels are readily prepared via a “click” reaction and exhibit a range of membrane activities consistent with the formation of ion channels in planar bilayer membranes. The durations of irregular and transient conductance events appear to follow a power-law scaling. [Link]

Skills

Our research straddles the traditional borders of science; we call ourselves physical organic chemists, and for the most part we use whatever methods it takes to get at the answer.  We use synthetic organic chemistry to generate the array of non-trivial compounds and electro-physiology techniques to characterize their behaviours in membranes.  Programming, statistics, and visualization help extract meaningful data.  The following sections describe what I do in some more details.

Research Overview
What I do in my research

 Chemistry

I worked on different classes of compounds in my career, including saccharides while in M. Pinto’s lab, aluminium carbenes with J. Clyburne, and small pharmaceuticals during a Process Chemistry co-op with Merck-Frosst.  For my PhD I worked on two main classes of compounds.  Both of them are amphiphiles (contains parts that are highly polar, and other parts which are non-polar).  One class of these consists of traditional small molecules, and the larger class are cyclodextrin conjugates of 2000–5000 amu.

Electrophysiology

Once compounds were made, their activities were examined using the voltage-clamp experiment.  Unlike normal “chemical” measurements where a large number of molecules is being looked at, this is a “single-molecule” (small groups of molecules in reality) method.  Conceptually it is quite simple: two compartments of electrolytes are separated by a membrane, and ion flow that occurs when a channel becomes “active” results in a small (sub-picoAmpere) but measurable current.


The analysis of the data, however, is not necessarily trivial, and to deal with the large data-sets in off-the-beaten-path ways, the tools will need to be developed.

Computational

I developed in-house tools for data analysis and exploration, and there my language of choice is Python.  It has great support for scientific analysis (SciPy/NumPy), plotting (matplotlib), and interaction (via Traits-Chaco).  With advances in browsers speed and support libraries, I’m learning to code in JavaScript/CoffeeScript and some of the applications thus developed may be ported so they can be (more-or-less) universally accessed without need to download tools.

Teaching

As a teaching assistant I’ve instructed and assessed laboratory work, facilitated help center, marked exams, as well as design and lead tutorials.  The courses I’ve taught in ranges from 1st to 3rd year, and includes courses in general chemistry, spectroscopy, physical chemistry, and organic chemistry.  As a substitute teacher I’ve also taught the International Baccalaureate curriculum at a United World College.  My teaching has been recognized at the department and university levels with Chemistry Excellence in Teaching Award as well as the Farquharson Award.

I participated and organized activities with the UVic Learning and Teaching Center that support and promote good teaching by teaching assistants.  These include conferences and workshops for professional development, the Instructional Skills Workshop, as well as a certificate for completing the Program in University Teaching.

I also run workshops on chemistry information literacy and LaTeX writing on official and unofficial basis.

[one_third][box] Curriculum vitae (PDF)[/box][/one_third]

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