My research interest in the past three years

It might be slightly weird that one's research interest is different from what has been done during one's PhD study, but this does happen to me. While I may not hold a chance to fulfil my dream, I just record here what I have read, learned and thought in spare time during the past three years.

Ideally I want to see scientific theories meet realistic demands. I believe that theoretical works hold the key to real breakthrough in life science, in the same way as the understanding of electromagnetic induction brought us into the electric era in the 19th century. With my background in population genetics and evolutionary game theory, I have long been looking for a research topic where theoretical thinking is appreciated and testable hypotheses can be generated, which may finally lead to solid rules for developing applications and solving realistic problems.

In 2009 I became interested in the topic where ecological and evolutionary theories are used to investigate the population dynamics of cells in a tumour tissue, where it sounds so naturally to regard cells as a population and cancerous cells are just like betrayers among the cooperative cells within a multi-cellular body. I read papers written by Robert Gatenby, Thomas Vincent and Thomas Pfeiffer talking about competition among cells based on their strategies of ATP production, which I think made a lot of sense. Especially I was interested in a few papers by Pfeiffer that pointed out the rate rather than efficiency of ATP production can be essential to the fitness of an individual cell. This really innovated my mind.

Meanwhile I came across another interesting topic, the conflict between nuclear and cytoplasmic genomes, elaborated in details by Steven Frank, which implied that even a single cell may show incomplete individuality. Because the fitness of mitochondrial genomes is not always 100% consistent with that of the nuclear genome in a cell, the two players, one of which (mtDNA) is actually a population composed of multiple mutually symmetric players, are always coping with each other, wherein various strategies may have emerged and survived/extinguished. The incomplete individuality of a single cell may be relevant to various diseases including cancer.

Since then I was thinking about synthesizing the two topics under one scheme, by using game theory at both inter- and intra-cellular levels simultaneously. However I did not persist in trying this as then I became busy with my PhD works.

Later in the end of 2010 I became interested in another topic, the control of cell fate decision governed by gene regulatory networks. I happened to read the articles written by Sui Huang (now in ISB Seattle), Stuart Kauffman and their co-workers on this topic, and I was quickly fascinated by the elegance of their theory and works. I learned mathematical tools to repeat and understand the modelling in their papers, and since then I have been learning more of dynamical systems and network theories. 

Earlier this year I got stuck with two basic questions: 1) how a system can travel from one attractor state to another (or to several possible attractor states in parallel) in a pre-determined order; 2) how the process of cell differentiation gets coordinated with decreasing cell proliferation in a somatic cell lineage. The two questions are again naturally related to cancer progression, indicating multiple possible accesses to carcinogenesis during various stages of cell development. I am very happy that one of Maximino Aldana's latest papers (DOI:10.1371/journal.pone.0042348) may have implied the answer to the second question, although still with a few steps away.

I think it is possible to combine the perspectives from both developmental and evolutionary biology one day to completely understand how cell differentiation is organized in metazoan and how cancer may emerge through various paths. My dream has been that I could play a role in those fields of research. However at the moment I can only do something within my own capability.

Now I have resumed working on the previous topic, looking into the inter-mitochondrial competition, cyto-nuclear conflict and inter-cellular competition simultaneously using game theory. The aim is to establish a model to find what kind of steady states may be achieved in single-cellular organisms, in normal somatic cells of multi-cellular organisms and in tumour cells. I have not composed the whole story yet but this may be the most reachable goal to me in the near future. I know I may not have a chance to work on it as my job, but I will keep doing this in my spare time.