Unified Theory of Circadian Clock

Experimental and Mathematical Analyses Relating Circadian Period and Phase of Entrainment in Neurospora crassa.1

A foundational work to debunk the dogma in the chronobiology field that phase of the entrainment is simply a reflection of the period; morning chronotype cannot be explained by a short period and evening chronotype a long period.

A Two-Step Model of Human Entrainment: A Quantitative Study of Circadian Period and Phase of Entrainment.2

The clock model that we developed in Neurospora system can be translated into that of the human.

A Unified Model for Entrainment by Circadian Clocks: Dynamic Circadian Integrated Response Characteristic (dCiRC).3

Mathematical and empirical study on developing a unified model to describe and predict the circadian clock’s behavior in constant and cycling environments.

Natural Variation of the Clock and Its Fitness Consequences

Inverted Race Tube Assay for Circadian Clock Studies of the Neurospora Accessions.4

An easy assay was developed to study the circadian rhythms in natural ecotypes of Neurospora. This simple assay made all my natural variation study of the Neurospora clocks possible.

Simple sequence repeats in Neurospora crassa: distribution, polymorphism and evolutionary inference.5

Genome-wide analysis of SSR as a molecular marker allowed all quantitative genetics study in my research program.

Simple sequence repeats provide a substrate for phenotypic variation in the Neurospora crassa circadian clock.6

Using the SSR markers, we analyzed the natural variation of circadian clock genes and its potential role for fitness.

Quantitative trait loci for the circadian clock in Neurospora crassa.7

Using the SSR markers, we performed QTL analysis for circadian period and phase phenotypes. We identified major QTL genes for clock traits.

Natural Variation of the Circadian Clock in Neurospora.8

A review paper on natural variation of circadian clocks.

Habitat-Specific Clock Variation and Its Consequence on Reproductive Fitness.9

Quantitative and molecular genetics study in characterizing habitat-specific clock variation to identify a gene whose adaptive variation caused fitness increase of a North American ecotype in natural habitat.

PKCdelta plays a role in both circadian and circannual rhythms.10

GWAS analysis on the photoperiodism in Drosophila melanogaster. Top 4 candidate genes are characterized on circadian and circannual rhythm phenotypes. Two mutant alleles of PKCdelta gene are characterized further.

Ecological and Applied Fungal Genetics

Neurospora, a potential fungal organism for experimental and evolutionary ecology.11

A review paper on the potential usage of the model fungal organism for addressing broader questions in evolutionary ecology.

Asexual and sexual developments of Neurospora crassa on natural substrata.12

Ironically, not much is known of the ecology of Neurospora, the model fungal organism. As far as I know, this is the first attempt to test the potential of Neurospora for ecological studies.

Advancement of Functional Genomics of a Model Species of Neurospora and Its Use for Ecological Genomics of Soil Fungi.13

A review paper on functional genomics approach for ecological studies using Neurospora.

Suppressing the Neurospora crassa circadian clock while maintaining light responsiveness in continuous stirred tank reactors.14

Circadian regulation could be hindrance for overexpression of a valuable metabolites. This study demonstrated that one could suppress circadian regulation in continuous bioreactors, which will allow to produce valuable metabolites in a controlled bio-reactor condition.

Controlled Growth of Nanostructured Biotemplates with Cobalt and Nitrogen Codoping as a Binderless Lithium-Ion Battery Anode.15

Neurospora mycelia could be used as a bio-battery.

Developing elite Neurospora crassa strains for cellulosic ethanol production using fungal breeding.16

Proof of concept in fungal breeding for improving fungal traits for economical biofuel production.

Quantitative trait loci (QTL) underlying phenotypic variation in bioethanol-related processes in Neurospora crassa.17

Quantitative genetics study to identify all genetic factors for traits in bioethanol production using Neurospora.

Roles of Ambient Light in Disease Development

Light regulation of asexual development in the rice blast fungus, Magnaporthe oryzae.18 

Fungi can ‘remember’ ambient light conditions. When the fungus grows under different light conditions few days, they develop differently to the same light condition depending on the previous light conditions they were exposed.

Genetic and molecular characterization of a blue light photoreceptor MGWC-1 in Magnaporth oryzae.19

The ambient light conditions determine the disease development of a plant. There is a disease-conducive ambient light condition and disease-suppressive light condition.

 

References

1          Lee, K., Shiva Kumar, P., McQuade, S., Lee, J. Y., Park, S., An, Z. & Piccoli, B. Experimental and Mathematical Analyses Relating Circadian Period and Phase of Entrainment in Neurospora crassa. J Biol Rhythms, 748730417738611, doi:10.1177/0748730417738611 (2017).

2          An, Z., Merrill, N. J., Lee, K., Robin, R., Hayat, A., Zapfe, O. & Piccoli, B. A Two-Step Model of Human Entrainment: A Quantitative Study of Circadian Period and Phase of Entrainment. Bull Math Biol 83, 12, doi:10.1007/s11538-020-00829-5 (2021).

3          An, Z., Piccoli, B., Merrow, M. & Lee, K. A Unified Model for Entrainment by Circadian Clocks: Dynamic Circadian Integrated Response Characteristic (dCiRC). Journal of biological rhythms 0, 07487304211069454, doi:10.1177/07487304211069454 (2022).

4          Park, S. & Lee, K. Inverted Race Tube Assay for Circadian Clock Studies of the Neurospora Accessions. Fungal Gen. Newsl. 51, 12-14 (2004).

5          Kim, T. S., Booth, J. G., Gauch, H. G., Jr., Sun, Q., Park, J., Lee, Y. H. & Lee, K. Simple sequence repeats in Neurospora crassa: distribution, polymorphism and evolutionary inference. BMC Genomics 9, 31, doi:10.1186/1471-2164-9-31 (2008).

6          Michael, T. P., Park, S., Kim, T. S., Booth, J., Byer, A., Sun, Q., Chory, J. & Lee, K. Simple sequence repeats provide a substrate for phenotypic variation in the Neurospora crassa circadian clock. PLoS One 2, e795, doi:10.1371/journal.pone.0000795 (2007).

7          Kim, T.-S., Logsdon, B. A., Park, S., Mezey, J. G. & Lee, K. Quantitative Trait Loci for the Circadian Clock in Neurospora crassa. Genetics 177, 2335-2347, doi:10.1534/genetics.107.077958 (2007).

8          Koritala, B. S. C. & Lee, K. in Adv. Genet. Vol. 99  (ed Stephen F. Goodwin)  1-37 (Academic Press, 2017).

9          Koritala, B. S. C., Wager, C., Waters, J. C., Pachucki, R., Piccoli, B., Feng, Y., Scheinfeldt, L. B., Shende, S. M., Park, S., Hozier, J. I., Lalakia, P., Kumar, D. & Lee, K. Habitat-Specific Clock Variation and Its Consequence on Reproductive Fitness. J Biol Rhythms 35, 134-144, doi:10.1177/0748730419896486 (2020).

10        Khaira, H., Patro, S. & Lee, K. Roles of PKCdelta in Photoperiod and Circadian Regulations in Drosophila melanogaster. bioRxiv, 2021.2009.2029.462474, doi:10.1101/2021.09.29.462474 (2022).

11        Lee, K. & Dighton, J. Neurospora, a potential fungal organism for experimental and evolutionary ecology. Fungal Biology Reviews 24, 85-89, doi:http://dx.doi.org/10.1016/j.fbr.2010.09.001 (2010).

12        Lee, K. Asexual and sexual developments of Neurospora crassa on natural substrata. Fungal Ecology 5, 223-229, doi:http://dx.doi.org/10.1016/j.funeco.2011.09.001 (2012).

13        Lee, K. & Dighton, J. in Genomics of Soil- and Plant-Associated Fungi Vol. 36 Soil Biology (eds Benjamin A. Horwitz, Prasun K. Mukherjee, Mala Mukherjee, & Christian P. Kubicek) Ch. 3, 29-44 (Springer Berlin Heidelberg, 2013).

14        Cockrell, A. L., Pirlo, R. K., Babson, D. M., Cusick, K. D., Soto, C. M., Petersen, E. R., Davis, M. J., Hong, C. I., Lee, K., Fitzgerald, L. A. & Biffinger, J. C. Suppressing the Neurospora crassa circadian clock while maintaining light responsiveness in continuous stirred tank reactors. Sci Rep 5, 10691, doi:10.1038/srep10691 (2015).

15        Huggins, T. M., Whiteley, J. M., Love, C. T., Lee, K., Lee, S. H., Ren, Z. J. & Biffinger, J. C. Controlled Growth of Nanostructured Biotemplates with Cobalt and Nitrogen Codoping as a Binderless Lithium-Ion Battery Anode. ACS Appl Mater Interfaces 8, 26868-26877, doi:10.1021/acsami.6b09300 (2016).

16        Waters, J. C., Nixon, A., Dwyer, M., Biffinger, J. C. & Lee, K. Developing elite Neurospora crassa strains for cellulosic ethanol production using fungal breeding. J Ind Microbiol Biotechnol 44, 1137-1144, doi:10.1007/s10295-017-1941-0 (2017).

17        Waters, J. C., Jhaveri, D., Biffinger, J. C. & Lee, K. Quantitative trait loci (QTL) underlying phenotypic variation in bioethanol-related processes in Neurospora crassa. PLoS One 15, e0221737, doi:10.1371/journal.pone.0221737 (2020).

18        Lee, K., Singh, P., Chung, W. C., Ash, J., Kim, T. S., Hang, L. & Park, S. Light regulation of asexual development in the rice blast fungus, Magnaporthe oryzae. Fungal Genet Biol 43, 694-706, doi:S1087-1845(06)00086-7 [pii]

10.1016/j.fgb.2006.04.005 (2006).

19        Kim, S., Singh, P., Park, J., Park, S., Friedman, A., Zheng, T., Lee, Y.-H. & Lee, K. Genetic and molecular characterization of a blue light photoreceptor MGWC-1 in Magnaporth oryzae. Fungal Genetics and Biology 48, 400-407 (2011).